Xu Jin, Qiu Yun
Department of Pharmacology, University of Maryland School of Medicine, Baltimore, MD, USA.
Asian J Urol. 2016 Oct;3(4):177-184. doi: 10.1016/j.ajur.2016.08.003. Epub 2016 Aug 20.
Prostate cancer (PCa) is one of the most lethal cancers in western countries. Androgen receptor (AR) signaling pathway plays a key role in PCa progression. Despite the initial effectiveness of androgen deprivation therapy (ADT) for treatment of patients with advanced PCa, most of them will develop resistance to ADT and progress to metastatic castration resistant prostate cancer (mCRPC). Constitutively transcriptional activated AR splice variants (AR-Vs) have emerged as critical players in the development and progression of mCRPC. Among AR-Vs identified to date, AR-V7 (a.k.a. AR3) is one of the most abundant and frequently found in both PCa cell lines and in human prostate tissues. Most of functional studies have been focused on AR-V7/AR3 and revealed its role in regulation of survival, growth, differentiation and migration in prostate cells. In this review, we will summarize our current understanding of regulation of expression and activity of AR-Vs in mCRPC.
前列腺癌(PCa)是西方国家最致命的癌症之一。雄激素受体(AR)信号通路在PCa进展中起关键作用。尽管雄激素剥夺疗法(ADT)对晚期PCa患者的治疗最初有效,但大多数患者会对ADT产生耐药性,并进展为转移性去势抵抗性前列腺癌(mCRPC)。组成型转录激活的AR剪接变体(AR-Vs)已成为mCRPC发生和发展的关键因素。在迄今为止鉴定出的AR-Vs中,AR-V7(又名AR3)是在PCa细胞系和人类前列腺组织中最丰富且最常发现的一种。大多数功能研究都集中在AR-V7/AR3上,并揭示了其在前列腺细胞存活、生长、分化和迁移调节中的作用。在本综述中,我们将总结目前对mCRPC中AR-Vs表达和活性调节的理解。