| Literature DB >> 20478527 |
Jindan Yu1, Jianjun Yu, Ram-Shankar Mani, Qi Cao, Chad J Brenner, Xuhong Cao, Xiaoju Wang, Longtao Wu, James Li, Ming Hu, Yusong Gong, Hong Cheng, Bharathi Laxman, Adaikkalam Vellaichamy, Sunita Shankar, Yong Li, Saravana M Dhanasekaran, Roger Morey, Terrence Barrette, Robert J Lonigro, Scott A Tomlins, Sooryanarayana Varambally, Zhaohui S Qin, Arul M Chinnaiyan.
Abstract
Chromosomal 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. (c) 2010 Elsevier Inc. All rights reserved.Entities:
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Year: 2010 PMID： 20478527 PMCID： PMC2874722 DOI： 10.1016/j.ccr.2010.03.018
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743