Negative regulation of the androgen receptor gene through a primate-specific androgen response element present in the 5' UTR.
Negative regulation of the androgen receptor gene through a primate-specific androgen response element present in the 5' UTR.
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DOI：
10.1007/s12672-014-0185-y
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发表时间：
2014-10
影响因子：
3
通讯作者：
McEwan IJ
中科院分区：
文献类型：
--
作者：
Hay CW;Watt K;Hunter I;Lavery DN;MacKenzie A;McEwan IJ
雄激素受体（AR）是一种广泛表达的配体激活的转录因子，其通过与正常组织和前列腺癌（PCa）中的雄激素反应元件（战神）结合来介导雄激素信号传导。在肿瘤内，AR的量在决定细胞生长、对治疗的抗性和进展至致命性去势复发性PCa中起着至关重要的作用，其中前列腺细胞似乎变得不依赖于雄激素类固醇。尽管AR在男性发育和生育力以及PCa发育的所有阶段中起着关键作用，但对AR表达的调控机制仍知之甚少。在这项工作中，我们描述了一个活跃的非共识雄激素反应元件（ARE）的5′ UTR的人AR基因。ARE在与活化的AR结合后抑制转录，并且这种下调通过突变破坏调节元件来缓解。此外，基因组区域的多个物种比较揭示了该ARE对灵长类动物是特异性的，从而得出结论，即在基于啮齿动物启动子研究阐明人AR在PCa中的作用时必须小心。本文的在线版本（doi：10.1007/s12672-014-0185-y）包含补充材料，可供授权用户使用。
The androgen receptor (AR) is a widely expressed ligand-activated transcription factor which mediates androgen signalling by binding to androgen response elements (AREs) in normal tissue and prostate cancer (PCa). Within tumours, the amount of AR plays a crucial role in determining cell growth, resistance to therapy and progression to fatal castrate recurrent PCa in which prostate cells appear to become independent of androgenic steroids. Despite the pivotal role of the AR in male development and fertility and all stages of PCa development, the mechanisms governing AR expression remain poorly understood. In this work, we describe an active nonconsensus androgen response element (ARE) in the 5′ UTR of the human AR gene. The ARE represses transcription upon binding of activated AR, and this downregulation is relieved by disruption of the regulatory element through mutation. Also, multiple species comparison of the genomic region reveals that this ARE is specific to primates, leading to the conclusion that care must be exercised when elucidating the operation of the human AR in PCa based upon rodent promoter studies. The online version of this article (doi:10.1007/s12672-014-0185-y) contains supplementary material, which is available to authorized users.
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影响因子：
3.5
作者：
Brodie, J;McEwan, IJ
通讯作者：
McEwan, IJ
影响因子：
50.3
作者：
Cai C;He HH;Chen S;Coleman I;Wang H;Fang Z;Chen S;Nelson PS;Liu XS;Brown M;Balk SP
通讯作者：
Balk SP
影响因子：
4.5
作者：
Francis JC;Thomsen MK;Taketo MM;Swain A
通讯作者：
Swain A
影响因子：
2.8
作者：
Isaacs, John T.;D'Antonio, Jason M.;Denmeade, Samuel R.
通讯作者：
Denmeade, Samuel R.
影响因子：
4.1
作者：
BLOK, LJ;THEMMEN, APN;GROOTEGOED, JA
通讯作者：
GROOTEGOED, JA