Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1.
Androgen receptor gene expression in prostate cancer is directly suppressed by the androgen receptor through recruitment of lysine-specific demethylase 1.
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DOI：
10.1016/j.ccr.2011.09.001
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发表时间：
2011-10-18
期刊：
影响因子：
50.3
通讯作者：
Balk SP
中科院分区：
文献类型：
--
作者：
Cai C;He HH;Chen S;Coleman I;Wang H;Fang Z;Chen S;Nelson PS;Liu XS;Brown M;Balk SP
雄激素受体（AR）在去势抵抗性前列腺癌（CRPC）中通过包括AR基因表达显著增加在内的机制被重新激活。我们确定了AR第二内含子中的增强子有助于CRPC中低雄激素水平下AR表达的增加。此外，在雄激素水平增加时，AR结合该位点并通过招募赖氨酸特异性脱甲基酶1（LSD 1）和H3K4me1，2脱甲基化来抑制AR基因表达。AR类似地抑制介导雄激素合成、DNA合成和增殖的多个基因的表达，同时刺激介导脂质和蛋白质生物合成的基因。CRPC中的雄激素水平似乎足以刺激增强子元件上的AR活性，而不是抑制子元件，导致AR和AR抑制基因的表达增加，从而促进细胞增殖。
Androgen receptor (AR) is reactivated in castration resistant prostate cancer (CRPC) through mechanisms including marked increases in AR gene expression. We identify an enhancer in the AR second intron contributing to increased AR expression at low androgen levels in CRPC. Moreover, at increased androgen levels the AR binds this site and represses AR gene expression through recruitment of lysine specific demethylase 1 (LSD1) and H3K4me1,2 demethylation. AR similarly represses expression of multiple genes mediating androgen synthesis, DNA synthesis and proliferation, while stimulating genes mediating lipid and protein biosynthesis. Androgen levels in CRPC appear adequate to stimulate AR activity on enhancer elements, but not suppressor elements, resulting in increased expression of AR and AR repressed genes that contribute to cellular proliferation.
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影响因子：
82.9
作者：
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通讯作者：
Sawyers, CL
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Garcia-Bassets, Ivan;Kwon, Young-Soo;Rosenfeld, Michael G.
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