Aberrant ERG Expression Cooperates with Loss of PTEN to Promote Cancer Progression in the Prostate

Overview

Journal Nat Genet

Specialty Genetics

Date 2009 Apr 28

PMID 19396168

Citations 350

Authors

Brett S Carver

Jennifer Tran

Anuradha Gopalan

Zhenbang Chen

Safa Shaikh

Arkaitz Carracedo

Andrea Alimonti

Caterina Nardella

Shohreh Varmeh

Peter T Scardino

Carlos Cordon-Cardo

William Gerald

Pier Paolo Pandolfi

Affiliations

Soon will be listed here.

Abstract

Chromosomal translocations involving the ERG locus are frequent events in human prostate cancer pathogenesis; however, the biological role of aberrant ERG expression is controversial. Here we show that aberrant expression of ERG is a progression event in prostate tumorigenesis. We find that prostate cancer specimens containing the TMPRSS2-ERG rearrangement are significantly enriched for loss of the tumor suppressor PTEN. In concordance with these findings, transgenic overexpression of ERG in mouse prostate tissue promotes marked acceleration and progression of high-grade prostatic intraepithelial neoplasia (HGPIN) to prostatic adenocarcinoma in a Pten heterozygous background. In vitro overexpression of ERG promotes cell migration, a property necessary for tumorigenesis, without affecting proliferation. ADAMTS1 and CXCR4, two candidate genes strongly associated with cell migration, were upregulated in the presence of ERG overexpression. Thus, ERG has a distinct role in prostate cancer progression and cooperates with PTEN haploinsufficiency to promote progression of HGPIN to invasive adenocarcinoma.

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