Coactivator selective regulation of androgen receptor activity.
Coactivator selective regulation of androgen receptor activity.
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DOI：
10.1016/j.steroids.2009.02.007
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发表时间：
2009-08
期刊：
影响因子：
2.7
通讯作者：
Weigel, Nancy L.
中科院分区：
文献类型：
--
作者：
Agoulnik, Irina U.;Weigel, Nancy L.
雄激素受体（AR）是一种配体激活的核受体，其调节转录并刺激雄激素依赖性前列腺癌的生长。为了调节转录，AR招募一系列修饰染色质并促进转录的共激活因子。然而，关于配体和靶基因对辅活化剂的特异性要求的信息是有限的。我们比较了p160共激活剂SRC-1和SRC-3/RAC 3与SRA（类固醇受体RNA激活剂）的作用。如预期的，所有三种在激动剂存在下共激活AR。然而，SRC-1或SRC-3的过度表达增加了对部分拮抗剂醋酸环丙孕酮的AR活性，而SRA在这些条件下不能刺激AR活性。使用siRNA来降低LNCaP细胞中这些辅激活因子的表达，我们还发现这些辅激活因子的启动子特异性要求。SRC-3是PSA、TMPRSS 2和PMEPA 1的最佳雄激素依赖性诱导所需的，而SRA仅是TMPRSS 2基因的最佳诱导所需的。这些数据表明，不同组的AR靶基因对共激活因子和对AR配体的反应有不同的要求。
The androgen receptor (AR) is a ligand activated nuclear receptor, which regulates transcription and stimulates growth of androgen dependent prostate cancer. To regulate transcription, AR recruits a series of coactivators that modify chromatin and facilitate transcription. However, information on ligand and target gene specific requirements for coactivators is limited. We compared the actions of the p160 coactivators SRC-1 and SRC-3/RAC3 with SRA (steroid receptor RNA activator). All three coactivate AR in the presence of agonist as expected. However, overexpression of either SRC-1 or SRC-3 increased AR activity in response to the partial antagonist, cyproterone acetate, whereas SRA was unable to stimulate AR activity under these conditions. Using siRNA to reduce expression of these coactivators in LNCaP cells, we also found promoter specific requirement for these coactivators. SRC-3 is required for optimal androgen dependent induction of PSA, TMPRSS2, and PMEPA1 whereas SRA is required only for optimal induction of the TMPRSS2 gene. These data indicate that different groups of AR target genes have distinct requirements for coactivators and response to AR ligands.
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影响因子：
--
作者：
Agoulnik, Irina U.;Bingman, William E., III;Weigel, Nancy L.
通讯作者：
Weigel, Nancy L.
影响因子：
11.2
作者：
Agoulnik, IU;Vaid, A;Weigel, NL
通讯作者：
Weigel, NL
影响因子：
11.2
作者：
Zhou, HJ;Yan, J;Tsai, NJ
通讯作者：
Tsai, NJ
影响因子：
56.9
作者：
Tomlins, SA;Rhodes, DR;Chinnaiyan, AM
通讯作者：
Chinnaiyan, AM
影响因子：
11.2
作者：
Yan, Jun;Yu, Cheng-Tai;Tsai, Ming-Jer
通讯作者：
Tsai, Ming-Jer