Department of Urology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Curr Cancer Drug Targets. 2011 Sep;11(7):870-81. doi: 10.2174/156800911796798904.
Androgens, acting through the androgen receptor (AR), are responsible for many male reproductive and nonreproductive functions. Moreover, aberrant androgen/AR signaling plays a critical role in androgen-dependent prostate cancer (PCa) as well as castration-resistant prostate cancer (CRPC). The formation of a productive AR transcriptional complex requires AR cofactors that interact functionally and structurally with the AR. Since the discovery of the first such cofactor in 1995, an ever increasing number of proteins have been identified as AR coactivators or corepressors. The expression and function of several AR cofactors have been investigated in PCa, and a clear link between AR cofactors and the development and progression of PCa has been identified. Recently, AR splice variants in CRPC were reported, which display significant constitutive activity in the absence of ligand. Then, this discovery revolutionized the concept of AR cofactors in CRPC. The current review aims to provide an overview of AR cofactor proteins in the context of PCa. In addition, we discuss the potential of AR cofactors as novel therapeutic targets for PCa, particularly for CRPC.
雄激素通过雄激素受体（AR）发挥作用，负责许多男性生殖和非生殖功能。此外，异常的雄激素/AR 信号在雄激素依赖性前列腺癌（PCa）以及去势抵抗性前列腺癌（CRPC）中起着关键作用。产生有活性的 AR 转录复合物需要 AR 辅助因子，这些辅助因子在功能和结构上与 AR 相互作用。自 1995 年发现第一个这样的辅助因子以来，越来越多的蛋白质被鉴定为 AR 共激活剂或共抑制剂。已经在 PCa 中研究了几种 AR 辅助因子的表达和功能，并确定了 AR 辅助因子与 PCa 的发生和进展之间的明确联系。最近，在 CRPC 中报道了 AR 剪接变体，它们在没有配体的情况下显示出显著的组成型活性。然后，这一发现彻底改变了 CRPC 中 AR 辅助因子的概念。本综述旨在概述 PCa 中 AR 辅助因子蛋白的情况。此外，我们还讨论了 AR 辅助因子作为 PCa 的新型治疗靶点的潜力，特别是对 CRPC。
