The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer.
The convergence of DNA damage checkpoint pathways and androgen receptor signaling in prostate cancer.
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DOI：
10.1530/erc-14-0217
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发表时间：
2014-10
影响因子：
3.9
通讯作者：
Gioeli D
中科院分区：
文献类型：
--
作者：
Ta HQ;Gioeli D
越来越清楚的是，去势抵抗性前列腺癌依赖于雄激素受体。这导致了减少内源性类固醇激素产生的抗雄激素疗法的使用以及雄激素受体拮抗剂的使用。然而，雄激素受体并不单独起作用，而是与细胞信号蛋白的环境整合以影响细胞生物学。众所周知，癌症是一种遗传疾病，由突变和染色体易位的积累引起，使癌细胞能够存活，增殖和扩散。为了维持基因组的完整性，存在保守的检查点信号传导途径以促进细胞周期延迟、DNA修复和/或响应于DNA损伤的凋亡。雄激素受体与这些DNA损伤反应蛋白相互作用，影响这些DNA损伤反应蛋白并受其影响。这篇综述将集中在前列腺癌中检查点信号和雄激素受体之间的联系。我们将描述什么是已知的检查点信号的组成部分如何调节雄激素受体的活性和什么问题仍然面临的领域。
It is increasingly clear that Castration Resistant Prostate Cancer is dependent on the Androgen Receptor. This has led to the use of anti-androgen therapies that reduce endogenous steroid hormone production as well as the use of androgen receptor antagonists. However, the androgen receptor does not act in isolation and integrates with a milieu of cell signaling proteins to affect cell biology. It is well established that cancer is a genetic disease resulting from the accumulation of mutations and chromosomal translocations that enables cancer cells to survive, proliferate, and disseminate. To maintain genomic integrity, there exists conserved checkpoint signaling pathways to facilitate cell cycle delay, DNA repair, and/or apoptosis in response to DNA damage. The androgen receptor interacts with, affects, and is affected by these DNA damage response proteins. This review will focus on the connections between checkpoint signaling and the androgen receptor in prostate cancer. We will describe what is known about how components of checkpoint signaling regulate androgen receptor activity and what questions still face the field.