PT  - JOURNAL ARTICLE
AU  - Mani, Ram-Shankar
AU  - Iyer, Matthew K.
AU  - Cao, Qi
AU  - Brenner, J. Chad
AU  - Wang, Lei
AU  - Ghosh, Aparna
AU  - Cao, Xuhong
AU  - Lonigro, Robert J.
AU  - Tomlins, Scott A.
AU  - Varambally, Sooryanarayana
AU  - Chinnaiyan, Arul M.
TI  - TMPRSS2–ERG-Mediated Feed-Forward Regulation of Wild-Type ERG in Human Prostate Cancers
AID  - 10.1158/0008-5472.CAN-11-0876
DP  - 2011 Aug 15
TA  - Cancer Research
PG  - 5387--5392
VI  - 71
IP  - 16
4099  - http://cancerres.aacrjournals.org/content/71/16/5387.short
4100  - http://cancerres.aacrjournals.org/content/71/16/5387.full
SO  - Cancer Res2011 Aug 15; 71
AB  - Recurrent gene fusions involving ETS family genes are a distinguishing feature of human prostate cancers, with TMPRSS2–ERG fusions representing the most common subtype. The TMPRSS2–ERG fusion transcript and its splice variants are well characterized in prostate cancers; however, not much is known about the levels and regulation of wild-type ERG. By employing an integrative approach, we show that the TMPRSS2–ERG gene fusion product binds to the ERG locus and drives the overexpression of wild-type ERG in prostate cancers. Knockdown of TMPRSS2–ERG in VCaP cells resulted in the downregulation of wild-type ERG transcription, whereas stable overexpression of TMPRSS2–ERG in the gene fusion-negative PC3 cells was associated with the upregulation of wild-type ERG transcript. Further, androgen signaling-mediated upregulation of TMPRSS2–ERG resulted in the concomitant upregulation of wild-type ERG transcription in VCaP cells. The loss of wild-type ERG expression was associated with a decrease in the invasive potential of VCaP cells. Importantly, 38% of clinically localized prostate cancers and 27% of metastatic prostate cancers harboring the TMPRSS2–ERG gene fusions exhibited overexpression of wild-type ERG. Taken together, these results provide novel insights into the regulation of ERG in human prostate cancers. Cancer Res; 71(16); 5387–92. ©2011 AACR.