An Integrated Network of Androgen Receptor, Polycomb, and TMPRSS2-ERG Gene Fusions in Prostate Cancer Progression

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2010 May 19

PMID 20478527

Citations 495

Authors

Jindan Yu

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

Affiliations

Soon will be listed here.

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.

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