Transcriptional regulation of the TGF-β1 promoter by androgen receptor
Transcriptional regulation of the TGF-β1 promoter by androgen receptor
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DOI：
10.1042/bj20080651
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发表时间：
2008-12-15
影响因子：
4.1
通讯作者：
Wang, Zhengxin
中科院分区：
文献类型：
--
作者：
Qi, Wei;Gao, Shen;Wang, Zhengxin
TGF（转化生长因子）- β 1是一种影响多种组织内平衡过程的多功能细胞因子。tgf - β 1在前列腺中的表达受到雄激素的抑制，而在高转移性前列腺癌细胞中，其表达则受到雄激素的增强。在这里，我们研究了前列腺癌细胞中雄激素对人tgf - β 1启动子活性的调节。全长（-3363至+110）启动子在表达AR（雄激素受体）的PC3mm2细胞中显示出高水平的活性。进一步的缺失分析显示，启动子中有三个远端和三个近端AREs（雄激素反应元件）。凝胶位移和足迹分析表明，这些AREs与AR的dna结合区域发生物理相互作用。染色质免疫沉淀分析显示，AR的雄激素依赖性募集到tgf - β 1基因的含are区域。更重要的是，在tgf - β 1启动子中检测到阴性ARE。阳性和阴性AREs都在雄激素调节的tgf - β 1启动子转录中起作用。这些发现表明，雄激素信号可能在不同的信号或不同的环境条件下正或负调节tgf - β 1的表达。
TGF (transforming growth factor)-beta 1 is a multifunctional cytokine that influences homoeostatic processes of various tissues. TGF-beta 1 expression is inhibited by androgens in the prostate gland, whereas its expression is enhanced by androgens in highly metastatic prostate cancer cells. Here, we examined regulation of human TGF-beta 1 promoter activity by androgen in prostate cancer cells. The full-length (-3363 to +110) promoter showed a high level of activity in response to androgen in PC3mm2 cells expressing AR (androgen receptor). Further deletion analysis revealed three distal and three proximal AREs (androgen-response elements) in the promoter. Gel-shift and footprint assays show that these AREs physically interact with the DNA-binding domain of AR. Chromatin immunoprecipitation assays revealed the androgen-dependent recruitment of AR to the ARE-containing regions of the TGF-beta 1 gene. More importantly, a negative ARE was detected in the TGF-beta 1 promoter. Both positive and negative AREs are functional in the androgen-regulated transcription of the TGF-beta 1 promoter. These findings imply that androgen signalling may positively or negatively regulate TGF-beta 1 expression in response to various signals or under different environmental conditions.