Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate

  • 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

Research output: Contribution to journalArticlepeer-review

556 Scopus citations

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.

Original languageEnglish
Pages (from-to)619-624
Number of pages6
JournalNature Genetics
Volume41
Issue number5
DOIs
StatePublished - May 2009
Externally publishedYes

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