Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate.
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.
Carver
Brett S
BS
Cancer Biology and Genetics Program, Sloan-Kettering Institute, New York, New York, USA.
Tran
Jennifer
J
Gopalan
Anuradha
A
Chen
Zhenbang
Z
Shaikh
Safa
S
Carracedo
Arkaitz
A
Alimonti
Andrea
A
Nardella
Caterina
C
Varmeh
Shohreh
S
Scardino
Peter T
PT
Cordon-Cardo
Carlos
C
Gerald
William
W
Pandolfi
Pier Paolo
PP
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
C072312:ERG protein, human; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D051059:PTEN Phosphohydrolase