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

C. Sun, A. Dobi, A. Mohamed, H. Li, R. L. Thangapazham, B. Furusato, S. Shaheduzzaman, S. H. Tan, G. Vaidyanathan, E. Whitman, D. J. Hawksworth, Y. Chen, M. Nau, V. Patel, M. Vahey, J. S. Gutkind, T. Sreenath, G. Petrovics, I. A. Sesterhenn, D. G. McLeodS. Srivastava

Research output: Contribution to journalArticlepeer-review

Abstract

The high prevalence of TMPRSS2-ERG rearrangements (∼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.

Original languageEnglish (US)
Pages (from-to)5348-5353
Number of pages6
JournalOncogene
Volume27
Issue number40
DOIs
StatePublished - Sep 11 2008

Keywords

  • C-MYC
  • ERG
  • Oncogene
  • PSA
  • Prostate cancer
  • TMPRSS2-ERG

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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