Daniels Garrett, Pei Zhiheng, Logan Susan K, Lee Peng
Department of Pathology, New York University School of Medicine New York, NY, USA.
Department of Pathology, New York University School of Medicine New York, NY, USA ; NYU Cancer Institute, New York University School of Medicine New York, NY, USA ; New York Harbor Healthcare System, New York University School of Medicine New York, NY, USA.
Am J Clin Exp Urol. 2013 Dec 25;1(1):25-9. eCollection 2013.
Androgen receptor (AR) plays an important role in the tumorigenesis and progression of prostate cancer (PCa), and is the primary therapeutic target for PCa treatment. AR activity can be regulated via phosphorylation at multiple phosphorylation sites within the protein. Modifications by phosphorylation alter AR function, including its cellular localization, stability and transcriptional activity, ultimately leading to changes in cancer cell biology and disease progression. Here we present a brief overview of AR phosphorylation sites in PCa, focusing on functional roles of phospho-AR (p-AR) species, relevance in PCa disease progression, and potential as biomarkers and/or therapeutic targets through the use of kinase inhibitors. Additionally, recent evidence has shown the important role of AR activity in the cancer associated stroma on PCa growth and progression. The phosphorylation status of epithelial and stromal AR may be distinct; however, the current data available on stromal AR phosphorylation is limited. Further research will determine global view on the synergistic effects of phosphorylation across multiple AR sites in both epithelial and stromal cells and validate whether together they can be used as prognostic markers and/or effective therapeutic targets for PCa.
雄激素受体（AR）在前列腺癌（PCa）的发生和发展中起着重要作用，并且是PCa治疗的主要靶点。AR活性可通过该蛋白内多个磷酸化位点的磷酸化作用来调节。磷酸化修饰会改变AR的功能，包括其细胞定位、稳定性和转录活性，最终导致癌细胞生物学特性和疾病进展的变化。在此，我们简要概述PCa中AR的磷酸化位点，重点关注磷酸化AR（p-AR）亚型的功能作用、与PCa疾病进展的相关性以及通过使用激酶抑制剂作为生物标志物和/或治疗靶点的潜力。此外，最近的证据表明AR活性在癌症相关基质中对PCa生长和进展具有重要作用。上皮和基质AR的磷酸化状态可能不同；然而，目前关于基质AR磷酸化的可用数据有限。进一步的研究将确定上皮和基质细胞中多个AR位点磷酸化协同作用的整体情况，并验证它们是否可共同用作PCa的预后标志物和/或有效的治疗靶点。
