Induction of prostatic intraepithelial neoplasia and modulation of androgen receptor by ETS variant 1/ETS-related protein 81

Sook Shin, Tae Dong Kim, Jin Fang, Jan M. Van Deursen, Scott M. Dehm, Donald J. Tindall, Joseph P. Grande, Jan Marie Munz, George Vasmatzis, Ralf Janknecht

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

ETS variant 1 (ETV1), also known as ETS-related protein 81, is overexpressed in prostate tumors, but whether and how this transcription factor affects tumorigenesis has remained elusive. Here, we show that ETV1 is primarily overexpressed in the most aggressive human prostate tumors. Transgenic ETV1 mice developed prostatic intraepithelial neoplasia as well as hyperplasia/neoplasia in seminal vesicles. Moreover, ETV1 cooperated with the androgen receptor (AR) to bind to the prostate-specific antigen enhancer and stimulate gene transcription. Consistent with its ability to physically interact with AR, ETV1 rendered an ETV1 bindingsite-driven reporter androgen inducible, and, on the other hand, ETV1 super-induced transcription from an AR bindingsite on androgen stimulation. In conclusion, our study substantiates that ETV1 overexpression is an underlyingcause in the development of prostate and possibly also seminal vesicle cancer. Its interaction with and activation of AR provides a molecular mechanism on how ETV1 exerts its deleterious function. Thus, inhibiting ET V1 or blockingits interaction with AR may represent novel strategies in prostate cancer therapy.

Original languageEnglish (US)
Pages (from-to)8102-8110
Number of pages9
JournalCancer research
Volume69
Issue number20
DOIs
StatePublished - Oct 15 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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