title: Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
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.
authors.affiliation: Cancer Biology and Genetics Program, Sloan-Kettering Institute, New York, New York, USA.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Carver
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tran
authors.forename: Anuradha
authors.initials: A
authors.lastname: Gopalan
authors.forename: Zhenbang
authors.initials: Z
authors.lastname: Chen
authors.forename: Safa
authors.initials: S
authors.lastname: Shaikh
authors.forename: Arkaitz
authors.initials: A
authors.lastname: Carracedo
authors.forename: Andrea
authors.initials: A
authors.lastname: Alimonti
authors.forename: Caterina
authors.initials: C
authors.lastname: Nardella
authors.forename: Shohreh
authors.initials: S
authors.lastname: Varmeh
authors.forename: Peter T
authors.initials: PT
authors.lastname: Scardino
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: William
authors.initials: W
authors.lastname: Gerald
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D000071230:Transcriptional Regulator ERG
chemical_list: C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase