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

被引：642

作者：

Yu, Jindan ^{[1
,3
,6
,7
]}

Yu, Jianjun ^{[1
,3
]}

Mani, Ram-Shankar ^{[1
,3
]}

Cao, Qi ^{[1
,3
]}

Brenner, Chad J. ^{[1
,3
]}

Cao, Xuhong ^{[1
,2
,3
]}

Wang, Xiaoju ^{[1
,3
]}

Wu, Longtao ^{[7
]}

Li, James ^{[1
,3
]}

Hu, Ming ^{[1
,5
]}

Gong, Yusong ^{[1
,3
]}

Cheng, Hong ^{[1
,3
]}

Laxman, Bharathi ^{[1
,3
]}

Vellaichamy, Adaikkalam ^{[1
,3
]}

Shankar, Sunita ^{[1
,3
]}

Li, Yong ^{[1
,3
]}

Dhanasekaran, Saravana M. ^{[1
,3
]}

Morey, Roger ^{[1
,3
]}

Barrette, Terrence ^{[1
,3
]}

Lonigro, Robert J. ^{[1
,6
]}

Tomlins, Scott A. ^{[1
,3
]}

Varambally, Sooryanarayana ^{[1
,3
,6
]}

Qin, Zhaohui S. ^{[5
]}

Chinnaiyan, Arul M. ^{[1
,2
,3
,4
,6
]}

机构：

[1] Univ Michigan, Sch Med, Michigan Ctr Translat Pathol, Ann Arbor, MI 48109 USA

[2] Univ Michigan, Sch Med, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA

[3] Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA

[4] Univ Michigan, Sch Med, Dept Urol, Ann Arbor, MI 48109 USA

[5] Univ Michigan, Sch Med, Dept Biostat, Ann Arbor, MI 48109 USA

[6] Univ Michigan, Sch Med, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA

[7] Northwestern Univ, Feinberg Med Sch, Robert H Lurie Comprehens Canc Ctr, Div Hematol Oncol, Chicago, IL 60611 USA

来源：

CANCER CELL | 2010年 / 17卷 / 05期

关键词：

EMBRYONIC STEM-CELLS; GROUP PROTEIN EZH2; TRANSCRIPTION FACTOR; DEVELOPMENTAL REGULATORS; BINDING SITES; ETS FAMILY; E-CADHERIN; REPRESSION; EXPRESSION; GENOME;

D O I：

10.1016/j.ccr.2010.03.018

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：443 / 454

页数：12

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