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

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Rae JM, Johnson MD, Cordero KE, Scheys JO, Larios JM, Gottardis MM, Pienta KJ, Lippman ME

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

Prostate. 2006 Jun 1;66(8):886-94.

PubMed ID

16496412 [ View in PubMed

]

Abstract

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.