Androgen receptor signaling in prostate cancer development and progression.
Androgen receptor signaling in prostate cancer development and progression.
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DOI：
10.4103/1477-3163.83937
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发表时间：
2011
影响因子：
--
通讯作者：
Tindall DJ
中科院分区：
文献类型：
--
作者：
Lonergan PE;Tindall DJ
雄激素受体（AR）信号传导轴在前列腺的发育、功能和稳态中起着关键作用。AR的经典作用是通过AR核转位、与靶基因上的雄激素反应元件结合以及转录因子的募集或串扰来调节基因转录过程。前列腺癌的发生和进展也独特地依赖于AR。雄激素剥夺疗法仍然是治疗晚期前列腺癌的标准护理。尽管最初的反应良好，但几乎所有患者都不可避免地发展为更具侵略性的去势抵抗表型。现在有相当多的证据支持去势抵抗性前列腺癌（CRPC）的发生与AR的持续反式激活存在因果关系的概念。了解AR信号传导在CRPC进展中的关键事件和复杂性对于开发成功的未来疗法至关重要。本文综述了AR结构和信号在前列腺癌进展中的作用，特别关注AR在CRPC中的作用的最新发现。这些研究结果的临床意义和未来研究的潜在方向也被概述。
The androgen receptor (AR) signaling axis plays a critical role in the development, function and homeostasis of the prostate. The classical action of AR is to regulate gene transcriptional processes via AR nuclear translocation, binding to androgen response elements on target genes and recruitment of, or crosstalk with, transcription factors. Prostate cancer initiation and progression is also uniquely dependent on AR. Androgen deprivation therapy remains the standard of care for treatment of advanced prostate cancer. Despite an initial favorable response, almost all patients invariably progress to a more aggressive, castrate-resistant phenotype. Considerable evidence now supports the concept that development of castrate-resistant prostate cancer (CRPC) is causally related to continued transactivation of AR. Understanding the critical events and complexities of AR signaling in the progression to CRPC is essential in developing successful future therapies. This review provides a synopsis of AR structure and signaling in prostate cancer progression, with a special focus on recent findings on the role of AR in CRPC. Clinical implications of these findings and potential directions for future research are also outlined.