Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate Academic Article uri icon

Overview

MeSH Major

  • PTEN Phosphohydrolase
  • Prostate
  • Prostatic Neoplasms
  • Trans-Activators

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.

publication date

  • May 2009

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC2835150

Digital Object Identifier (DOI)

  • 10.1038/ng.370

PubMed ID

  • 19396168

Additional Document Info

start page

  • 619

end page

  • 24

volume

  • 41

number

  • 5