TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation

被引：186

作者：

Sun, C. ^{[1
]}

Dobi, A. ^{[1
,6
]}

Mohamed, A. ^{[1
]}

Li, H. ^{[1
]}

Thangapazham, R. L. ^{[1
]}

Furusato, B. ^{[1
,2
]}

Shaheduzzaman, S. ^{[1
]}

Tan, S-H ^{[1
]}

Vaidyanathan, G. ^{[1
]}

Whitman, E. ^{[1
,3
]}

Hawksworth, D. J. ^{[1
,3
]}

Chen, Y. ^{[1
]}

Nau, M. ^{[4
]}

Patel, V. ^{[5
]}

Vahey, M. ^{[4
]}

Gutkind, J. S. ^{[5
]}

Sreenath, T. ^{[1
]}

Petrovics, G. ^{[1
]}

Sesterhenn, I. A. ^{[2
,6
]}

McLeod, D. G. ^{[1
,3
,6
]}

Srivastava, S. ^{[1
,6
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Ctr Prostate Dis Res, Dept Surg, Rockville, MD 20852 USA

[2] Armed Forces Inst Pathol, Dept Genitourinary Pathol, Washington, DC 20306 USA

[3] Walter Reed Army Med Ctr, Urol Serv, Dept Surg, Washington, DC 20307 USA

[4] Walter Reed Army Inst Res, Div Retrovirol, Rockville, MD USA

[5] Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, Natl Inst Hlth, Bethesda, MD USA

[6] US Mil Canc Inst, Washington, DC USA

来源：

ONCOGENE | 2008年 / 27卷 / 40期

关键词：

ERG; prostate cancer; oncogene; C-MYC; PSA; TMPRSS2-ERG;

D O I：

10.1038/onc.2008.183

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The high prevalence of TMPRSS2-ERG rearrangements (similar to 60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

引用

页码：5348 / 5353

页数：6

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