Transmembrane protease serine 2: Difference between revisions
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=== Prostate cancer === | === Prostate cancer === | ||
Prostate cancer (PC) is the most common form of cancer found in American men and the second leading cause of cancer death. <ref>DOI 10.4172/1948-5956.1000119</ref> | Prostate cancer (PC) is the most common form of cancer found in American men and the second leading cause of cancer death. <ref>DOI 10.4172/1948-5956.1000119</ref> This means that approximately 28.5% of cancers and 3.5% of cancer related deaths in men are due to PC. | ||
The most common chromosomal aberration causing this pathology is the fusion of the the promoter of transmembrane protease, serine 2 (TMPRSS2) gene and the coding sequence of the erythroblastosis virus E26 (Ets) gene family members. Ets family members are oncogenic transcription factors. Therefore, the fusion of these genes leads to the production of Ets transcription factors under the control of the androgen sensitive promoter elements of TMPRSS2. | The most common chromosomal aberration causing this pathology is the fusion of the the promoter of transmembrane protease, serine 2 (TMPRSS2) gene and the coding sequence of the erythroblastosis virus E26 (Ets) gene family members. <ref>DOI 10.1126/science.1117679</ref> Ets family members are oncogenic transcription factors. <ref>DOI 10.1038/sj.onc.1201868</ref> Therefore, the fusion of these genes leads to the production of Ets transcription factors under the control of the androgen sensitive promoter elements of TMPRSS2. | ||
The most common of these fusions is with ERG (erythroblast-specific-related gene), a member of the Ets family, resulting in the TMPRSS2-ERG fusion. The TMPRSS2-ERG fusion has been identified in approximately 50% of PC cases. | The most common of these fusions is with ERG (erythroblast-specific-related gene), a member of the Ets family, resulting in the TMPRSS2-ERG fusion. The TMPRSS2-ERG fusion has been identified in approximately 50% of PC cases. <ref>DOI 10.1016/j.ccr.2010.03.018</ref> | ||
The mutation occurs through chromosomal translocation or intergenic deletion, with both genes on the same arm of chromosome 21, and results in overexpression of chimeric mRNA of ERG in response to androgens. | |||
The coding sequence of TMPRSS2 is not involved in the gene fusion. Consequently, there is no resultant recombinant protein for the TMPRSS2-ETS gene fusion and the promoterless copy of TMPRSS2 is silenced. | |||
There is impairment of apoptosis in TMPRSS2-ERG posi�tive cancer cells,37 possibly due to disruption of the intracellular death domain or decoy receptors. <ref>DOI 10.1186/1475-2867-14-34 </ref> | |||
The high prevalence of these gene fusions, in particular TMPRSS2-ERG, makes them attractive as potential diagnostic and prognostic indicators, as well as making them a potential target for tailored therapies. | |||
=== Viral entry === | === Viral entry === | ||
