ERG cooperates with androgen receptor in regulating trefoil factor 3 in prostate cancer disease progression. Academic Article uri icon

Overview

abstract

  • To elucidate the role of ETS gene fusions in castration-resistant prostate cancer (CRPC), we characterized the transcriptome of 54 CRPC tumor samples from men with locally advanced or metastatic disease. Trefoil factor 3 (TFF3) emerged as the most highly differentially regulated gene with respect to ERG rearrangement status and resistance to hormone ablation therapy. Conventional chromatin immunoprecipitation (ChIP)-polymerase chain reaction and ChIP followed by DNA sequencing (ChIP-seq) revealed direct binding of ERG to ETS binding sites in the TFF3 promoter in ERG-rearranged prostate cancer cell lines. These results were confirmed in ERG-rearranged hormone-naive prostate cancer (HNPC) and CRPC tissue samples. Functional studies demonstrated that ERG has an inhibitory effect on TFF3 expression in hormone-naive cancer but not in the castration-resistant state. In addition, we provide evidence suggesting an effect of androgen receptor signaling on ERG-regulated TFF3 expression. Furthermore, TFF3 overexpression enhances ERG-mediated cell invasion in CRPC prostate cancer cells. Taken together, our findings reveal a novel mechanism for enhanced tumor cell aggressiveness resulting from ERG rearrangement in the castration-resistant setting through TFF3 gene expression.

authors

  • Rickman, David S.
  • Chen, Ying-Bei
  • Banerjee, Samprit
  • Pan, Yihang
  • Yu, Jindan
  • Vuong, Terry
  • Perner, Sven
  • Lafargue, Christopher J
  • Mertz, Kirsten D
  • Setlur, Sunita R
  • Sircar, Kanishka
  • Chinnaiyan, Arul M
  • Bismar, Tarek A
  • Rubin, Mark A
  • Demichelis, Francesca

publication date

  • December 1, 2010

Research

keywords

  • Peptides
  • Prostatic Neoplasms
  • Receptors, Androgen
  • Trans-Activators

Identity

PubMed Central ID

  • PMC3003138

Scopus Document Identifier

  • 78649890593

Digital Object Identifier (DOI)

  • 10.1593/neo.10866

PubMed ID

  • 21170267

Additional Document Info

volume

  • 12

issue

  • 12