Letter abstract
Nature Genetics 41, 619 - 624 (2009)
Published online: 26 April 2009 | doi:10.1038/ng.370
Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate
Brett S Carver1,2, Jennifer Tran1, Anuradha Gopalan3, Zhenbang Chen1,4, Safa Shaikh2, Arkaitz Carracedo1,4, Andrea Alimonti1,4, Caterina Nardella1,4, Shohreh Varmeh1,4, Peter T Scardino2, Carlos Cordon-Cardo5, William Gerald3 & Pier Paolo Pandolfi1,3,4
Chromosomal translocations involving the ERG locus are frequent events in human prostate cancer pathogenesis; however, the biological role of aberrant ERG expression is controversial1. 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.
- Cancer Biology and Genetics Program, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
- Department of Surgery, Division of Urology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
- Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
- Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of Medicine and Pathology, Harvard Medical School, Boston, Massachusetts, USA.
- Department of Pathology, Columbia University, New York, New York, USA.
Correspondence to: Pier Paolo Pandolfi1,3,4 e-mail: ppandolf@bidmc.harvard.edu
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