GREB1 is a novel androgen-regulated gene required for prostate cancer growth

Prostate. 2006 Jun 1;66(8):886-94. doi: 10.1002/pros.20403.


Background: Gene regulated in breast cancer 1 (GREB1) is a novel estrogen-regulated gene shown to play a pivotal role in hormone-stimulated breast cancer growth. GREB1 is expressed in the prostate and its putative promoter contains potential androgen receptor (AR) response elements.

Methods: We investigated the effects of androgens on GREB1 expression and its role in androgen-dependent prostate cancer growth.

Results: Real-time PCR demonstrated high level GREB1 expression in benign prostatic hypertrophy (BPH), localized prostate cancer (L-PCa), and hormone refractory prostate cancer (HR-PCa). Androgen treatment of AR-positive prostate cancer cells induced dose-dependent GREB1 expression, which was blocked by anti-androgens. AR binding to the GREB1 promoter was confirmed by chromatin immunoprecipitation (ChIP) assays. Suppression of GREB1 by RNA interference blocked androgen-stimulated LNCaP cell proliferation.

Conclusions: GREB1 is expressed in proliferating prostatic tissue and prostate cancer, is regulated by androgens, and suppression of GREB1 blocks androgen-induced growth suggesting GREB1 may be critically involved in prostate cancer proliferation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Chromatin Immunoprecipitation
  • DNA, Neoplasm / drug effects
  • DNA, Neoplasm / genetics
  • Dose-Response Relationship, Drug
  • Estrogens / pharmacology
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Male
  • Neoplasm Proteins / analysis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / physiology*
  • Neoplasms, Hormone-Dependent / chemistry
  • Neoplasms, Hormone-Dependent / genetics
  • Neoplasms, Hormone-Dependent / pathology
  • Neoplasms, Hormone-Dependent / physiopathology
  • Oligonucleotide Array Sequence Analysis
  • Prostatic Neoplasms / chemistry
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Prostatic Neoplasms / physiopathology*
  • RNA, Messenger / analysis
  • RNA, Messenger / genetics
  • RNA, Small Interfering / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction


  • Androgens
  • DNA, Neoplasm
  • Estrogens
  • GREB1 protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • RNA, Small Interfering