Rae James M, Johnson Michael D, Cordero Kevin E, Scheys Joshua O, Larios José M, Gottardis Marco M, Pienta Kenneth J, Lippman Marc E
Division of Hematology Oncology, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109, USA.
Prostate. 2006 Jun 1;66(8):886-94. doi: 10.1002/pros.20403.
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.
We investigated the effects of androgens on GREB1 expression and its role in androgen-dependent prostate cancer growth.
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.
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.
乳腺癌中调控基因1（GREB1）是一种新的雌激素调控基因，已证实在激素刺激的乳腺癌生长中起关键作用。GREB1在前列腺中表达，其假定启动子含有潜在的雄激素受体（AR）反应元件。
我们研究了雄激素对GREB1表达的影响及其在雄激素依赖性前列腺癌生长中的作用。
实时PCR显示良性前列腺增生（BPH）、局限性前列腺癌（L-PCa）和激素难治性前列腺癌（HR-PCa）中GREB1高水平表达。用雄激素处理AR阳性前列腺癌细胞可诱导GREB1表达呈剂量依赖性，而抗雄激素可阻断这种表达。通过染色质免疫沉淀（ChIP）分析证实AR与GREB1启动子结合。RNA干扰抑制GREB1可阻断雄激素刺激的LNCaP细胞增殖。
GREB1在增殖性前列腺组织和前列腺癌中表达，受雄激素调控，抑制GREB1可阻断雄激素诱导的生长，提示GREB1可能在前列腺癌增殖中起关键作用。
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