TMPRSS2-ERG fusion, a common genomic alteration in prostate cancer activates C-MYC and abrogates prostate epithelial differentiation.

Published

Journal Article

The high prevalence of TMPRSS2-ERG rearrangements ( approximately 60%) in prostate cancer (CaP) leads to androgenic induction of the ETS-related gene (ERG) expression. However, the biological functions of ERG overexpression in CaP remain to be understood. ERG knockdown in TMPRSS2-ERG expressing CaP cells induced striking morphological changes and inhibited cell growth both in cell culture and SCID mice. Evaluation of the transcriptome and specific gene promoters in ERG siRNA-treated cells and investigation of gene expression signatures of human prostate tumors revealed ERG-mediated activation of C-MYC oncogene and the repression of prostate epithelial differentiation genes (PSA and SLC45A3/Prostein). Taken together, these data combining cell culture and animal models and human prostate tumors reveal that ERG overexpression in prostate tumor cells may contribute to the neoplastic process by activating C-MYC and by abrogating prostate epithelial differentiation as indicated by prostate epithelial specific markers.

Full Text

Duke Authors

Cited Authors

  • Sun, C; Dobi, A; Mohamed, A; Li, H; Thangapazham, RL; Furusato, B; Shaheduzzaman, S; Tan, S-H; Vaidyanathan, G; Whitman, E; Hawksworth, DJ; Chen, Y; Nau, M; Patel, V; Vahey, M; Gutkind, JS; Sreenath, T; Petrovics, G; Sesterhenn, IA; McLeod, DG; Srivastava, S

Published Date

  • September 11, 2008

Published In

Volume / Issue

  • 27 / 40

Start / End Page

  • 5348 - 5353

PubMed ID

  • 18542058

Pubmed Central ID

  • 18542058

Electronic International Standard Serial Number (EISSN)

  • 1476-5594

Digital Object Identifier (DOI)

  • 10.1038/onc.2008.183

Language

  • eng

Conference Location

  • England