Aberrant ERG expression cooperates with loss of PTEN to promote cancer progression in the prostate Journal Article
| Authors: | Carver, B. S.; Tran, J.; Gopalan, A.; Chen, Z.; Shaikh, S.; Carracedo, A.; Alimonti, A.; Nardella, C.; Varmeh, S.; Scardino, P. T.; Cordon-Cardo, C.; Gerald, W.; Pandolfi, P. P. |
| Article 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. © 2009 Nature America, Inc. All rights reserved. |
| Keywords: | immunohistochemistry; controlled study; human tissue; human cell; cancer growth; nonhuman; cell proliferation; mouse; phenotype; animals; mice; animal tissue; gene; cells, cultured; gene overexpression; gene expression; embryo; animal experiment; animal model; genotype; in vitro study; carcinogenesis; haplotype; prostatic neoplasms; tumor suppressor gene; prostate; heterozygosity; nucleotide sequence; phosphatidylinositol 3,4,5 trisphosphate 3 phosphatase; pten phosphohydrolase; transcription factor erg; oncogene proteins, fusion; cell migration; invasive carcinoma; adamts1 gene; cxcr4 gene; prostate adenocarcinoma; prostatic intraepithelial neoplasia; tumor promotion; upregulation; trans-activators |
| Journal Title: | Nature Genetics |
| Volume: | 41 |
| Issue: | 5 |
| ISSN: | 1061-4036 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2009-05-01 |
| Start Page: | 619 |
| End Page: | 624 |
| Language: | English |
| DOI: | 10.1038/ng.370 |
| PUBMED: | 19396168 |
| PROVIDER: | scopus |
| PMCID: | PMC2835150 |
| DOI/URL: | |
| Notes: | Correction issued, see DOI: 10.1038/s41588-020-0688-0 --- - "Cited By (since 1996): 41" - "Export Date: 30 November 2010" - "CODEN: NGENE" - "Source: Scopus" |
Altmetric
Citation Impact
BMJ Impact Analytics
MSK Authors
Related MSK Work