Proteopedia - User contributions [en]

Tamoxifen

2011-12-09T19:29:52Z

Andrea Danielle Merr: New page: <!-- Please use the "3D" button above this box to insert a Jmol applet (molecule) on this page. Or use the four-green-boxes-button to insert scrollable text adjacent to a Jmol applet. Che...

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that men and women with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.

== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|right|Prodrug Tamoxifen<ref> Wikipedia.org. http://en.wikipedia.org/wiki/Tamoxifen (accessed December 9th, 2011).</ref>]]

<references />

Sandbox Reserved 385

2011-12-09T19:28:53Z

Andrea Danielle Merr: /* Tamoxifen and the Estrogen Receptor */

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that men and women with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.

== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|right|Prodrug Tamoxifen<ref> Wikipedia.org. http://en.wikipedia.org/wiki/Tamoxifen (accessed December 9th, 2011).</ref>]]

<references />

Sandbox Reserved 385

2011-12-09T19:27:12Z

Andrea Danielle Merr: /* Tamoxifen and Breast Cancer */

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that men and women with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|right|Prodrug Tamoxifen<ref> Wikipedia.org. http://en.wikipedia.org/wiki/Tamoxifen (accessed December 9th, 2011).</ref>]]

<references />

Sandbox Reserved 385

2011-12-09T19:25:57Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|right|Prodrug Tamoxifen<ref> Wikipedia.org. http://en.wikipedia.org/wiki/Tamoxifen (accessed December 9th, 2011).</ref>]]

<references />

Sandbox Reserved 385

2011-12-09T19:25:06Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|right|Prodrug Tamoxifen|]]<ref> Wikipedia.org. http://en.wikipedia.org/wiki/Tamoxifen (accessed December 9th, 2011).</ref>

<references />

Sandbox Reserved 385

2011-12-09T19:23:58Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|left|Prodrug Tamoxifen|]]<ref>http://en.wikipedia.org/wiki/Tamoxifen</ref>

<references />

Sandbox Reserved 385

2011-12-09T19:22:36Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|left|Prodrug Tamoxifen|]]

<references />

Sandbox Reserved 385

2011-12-09T19:22:06Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png|thumb|400px|left|Prodrug Tamoxifen|<ref name="danielle"http://en.wikipedia.org/wiki/File:Tamoxifen_Structural_Formulae.png </ref>]]
==References==

<references />

Sandbox Reserved 385

2011-12-09T19:19:23Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer, are at a higher risk of the disease occurring.<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref> Estrogen is necessary in many areas of the body. It gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A recent hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer who undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring.<ref name="danielle" /> Tamoxifen binds to the ligand binging domain of the estrogen receptor, which leads to a conformational shift.<ref name="danielle" /> The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator.<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.</ref> This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a halt in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

[[Image:tam.png]]
==References==

<references />

File:Tam.png

2011-12-09T19:17:45Z

Andrea Danielle Merr:

from Wikipedia.org

File:Tam.png

2011-12-09T19:17:10Z

Andrea Danielle Merr: from Wikipedia.com

from Wikipedia.com

Sandbox Reserved 385

2011-12-02T21:44:38Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring<ref name="danielle">Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>
. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring<ref name="danielle" />
. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift<ref name="danielle" />
. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.
</ref>
. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

==References==

<references />

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{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>
. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>
. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>
. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.
</ref>
. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

==References==

<references />

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{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>

<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.
</ref>

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>
. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen activity in other cells, such as bone and liver cells.

==References==

<references />

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2011-12-02T21:33:33Z

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{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>

<ref>Pecorak, Sara, and Tom Susman. "Tamoxifen, Diethylstilbesterol and the Estrogen Receptor Ligand Binding Region." (04). Web. <http://biology.kenyon.edu/BMB/Chime2/2001/estrogen/FRAMES/start.htm>.
</ref>

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

==References==

<references />

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{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

<ref>Skafar, D., and S. Koide. "Understanding the Human Estrogen Receptor-alpha Using Targeted Mutagenesis." Molecular and Cellular Endocrinology 246.1-2 (2006): 83-90. </ref>

<ref>PMID:11807088</ref>

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

==References==

<references />

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Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

<ref> Bizzini B. Tetanus Toxin. Microbiological Reviews.1979 June;43(2):224-236.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281472/pdf/microrev00006-0112.pdf?tool=pmcentrez]</ref>

<ref>PMID:11807088</ref>

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

==References==

<references />

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2011-12-02T21:15:56Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

<ref> Bizzini B. Tetanus Toxin. Microbiological Reviews.1979 June;43(2):224-236.[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC281472/pdf/microrev00006-0112.pdf?tool=pmcentrez]</ref>

<ref>PMID:11807088</ref>

== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the <scene name='Sandbox_Reserved_385/12_helix_er/1'>helix 12</scene> to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing <scene name='Sandbox_Reserved_385/Test_scene/1'>helices 3, 8, and 11</scene> to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

==References==

<references />

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2011-12-01T01:20:14Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

[[Image:estrogen.PNG|The Drug Tamoxifen and the Tamoxifen-Estrogen Complex. The green area represents the change in signal loop due to conformational changes after ligand-binding of Tamoixfen.]]

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Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

[[Image:estrogen.PNG|Caption='The Drug Tamoxifen and the Tamoxifen-Estrogen Complex. The green area represents the change in signal loop due to conformational changes after ligand-binding of Tamoixfen'|]]

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Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

[[Image:estrogen.PNG|Caption=The Drug Tamoxifen and the Tamoxifen-Estrogen Complex. The green area represents the change in signal loop due to conformational changes after ligand-binding of Tamoixfen|]]

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Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

[[Image:estrogen.PNG|Caption=The Drug Tamoxifen and the Tamoxifen-Estrogen Complex. The green area represents the change in signal loop due to conformational changes after ligand-binding of Tamoixfen]]

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2011-12-01T01:12:54Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

[[Image:estrogen.PNG]]

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2011-12-01T01:08:46Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

<Structure load='3ert' size='500' frame='true' align='right' caption='Estrogen Receptor Ligand-Binding Domain in Complex with 4-Hydroxytamoxifen' scene='Insert optional scene name here' />

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

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2011-12-01T01:03:15Z

Andrea Danielle Merr:

{{Sandbox_Reserved_JMeans}}

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

User:Andrea Danielle Merr

2011-11-30T02:29:06Z

Andrea Danielle Merr:

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. With the coactivator site blocked, there is a hault in proliferation, meaning that there is no cell growth.
== Tamoxifen, the Drug ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone. The FDA approved this prodrug 30 years ago to prevent breast cancer in high risk patients. Tamoxifen is classfied as a Seletive Estrogen Receptor Modulator (SERM), meaning that it selectively blocks or activates the activity of estrogen on specific cells, such as breast cancer cells. While Tamoxifen is used to block estrogen acivity in breast cells, it also activates estrogen actrivity in other cells, such as bone and liver cells.

User:Andrea Danielle Merr

2011-11-30T02:21:58Z

Andrea Danielle Merr:

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. Conformational changes also occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend. These changes collectively block initiation of cell growth.

== ==
Tamoxifen is a precursor for the drug that binds to the estrogen receptor, making it a prodrug. The actual drug is 4-hydroxyltamoxifen, which has a greater affinity for the estrogen receptor than Tamoxifen alone.

User:Andrea Danielle Merr

2011-11-30T02:01:55Z

Andrea Danielle Merr:

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen and Breast Cancer ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. The drug Tamoxifen acts as a competitive inhibitor of estrogen and the estrogen receptor. Those with a higher risk of breast cancer that undergo treatment with Tamoxifen show low breast tissue density, which suggests a lower breast cancer risk. Tamoxifen is a smaller molecule that mimics the shape of estrogen, allowing it to bind tightly to the estrogen receptor.

== Tamoxifen and the Estrogen Receptor ==
Tamoxifen lacks the second OH group as well as a tail containing oxygen and nitrogen on the ring. Tamoxifen binds to the ligand binging domain of the estrogen, which leads to a conformational shift. The conformational change causes the helix 12 to shift into an adjacent coactivator. This site is essential for estrogen to do its job. Without the coactivator binding, the receptor remains inactive. The conformational changes occur due to the new hydrophobic interactions between helices 3 and 11. These newly formed hydrophobic interactions lead to a cascade effect of conformational changes across the molecule. The new side chain also causes conformational changes since one of the rings in Tamoxifen is shoved deeper into the pocket. Tamoxifen also provides one less hydrogen bond in the pocket compared to estrogen, causing helices 3, 8, and 11 to extend.

User:Andrea Danielle Merr

2011-11-30T01:55:15Z

Andrea Danielle Merr:

*[[User:AndreaDanielleMerr/Sandbox 1]]
== Tamoxifen ==
'''
Recent studies have shown that those with high estrogen levels, coupled with an already high risk of developing breast cancer are at a higher risk of the disease occurring. Estrogen is necessary in many areas of the body. Estrogen gives cells permission to grow, including cancer cells. Estrogen is regulated through an activated estrogen receptor transcription factor. These transcription factors in the higher risk patients can activate oncogenes that accelerate cancer cell growth. A new hypothesis suggests that a new way to prevent and treat breast cancer is to change the way estrogen binds to the receptor. Normally, estrogen binds to the estrogen receptor, allowing DNA to bind to it to it to initiate transcription of reproductive cycle-related genes. .<ref>PMID: 15610857 </ref>

User:Andrea Danielle Merr

2011-11-30T00:02:03Z

Andrea Danielle Merr:

*[[User:AndreaDanielleMerr/Sandbox 1]]