Author/Authors :
Yu، نويسنده , , Jindan and Yu، نويسنده , , Jianjun and Mani، نويسنده , , Ram-Shankar and Cao، نويسنده , , Qi and Brenner، نويسنده , , Chad J. and Cao، نويسنده , , Xuhong and Wang، نويسنده , , Xiaoju and Wu، نويسنده , , Longtao and Li، نويسنده , , James C Hu، نويسنده , , Ming and Gong، نويسنده , , Yusong and Cheng، نويسنده , , Hong and Laxman، نويسنده , , Bharathi and Vellaichamy، نويسنده , , Adaikkalam and Shankar، نويسنده , , Sunita and Li، نويسنده , , Yong and Dhanasekaran، نويسنده , , Saravana M. and Morey، نويسنده , , Roger and Barrette، نويسنده , , Terrence and Lonigro، نويسنده , , Robert J. and Tomlins، نويسنده , , Scott A. and Varambally، نويسنده , , Sooryanarayana and Qin، نويسنده , , Zhaohui S. and Chinnaiyan، نويسنده , , Arul M. Chinnaiyan، نويسنده ,
Abstract :
Summary
somal rearrangements fusing the androgen-regulated gene TMPRSS2 to the oncogenic ETS transcription factor ERG occur in approximately 50% of prostate cancers, but how the fusion products regulate prostate cancer remains unclear. Using chromatin immunoprecipitation coupled with massively parallel sequencing, we found that ERG disrupts androgen receptor (AR) signaling by inhibiting AR expression, binding to and inhibiting AR activity at gene-specific loci, and inducing repressive epigenetic programs via direct activation of the H3K27 methyltransferase EZH2, a Polycomb group protein. These findings provide a working model in which TMPRSS2-ERG plays a critical role in cancer progression by disrupting lineage-specific differentiation of the prostate and potentiating the EZH2-mediated dedifferentiation program.
