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Cancer Cell. 2010 May 18;17(5):443-54. doi: 10.1016/j.ccr.2010.03.018.

An integrated network of androgen receptor, polycomb, and TMPRSS2-ERG gene fusions in prostate cancer progression.

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1
Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

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.

PMID:
20478527
PMCID:
PMC2874722
DOI:
10.1016/j.ccr.2010.03.018
[Indexed for MEDLINE]
Free PMC Article

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