Sex Hormone Research Center, Department of Gastroenterology, Graduate Institute of Clinical Medical Science, China Medical University/Hospital, Taichung 404, Taiwan, Republic of China George Whipple Lab for Cancer Research, Departments of Pathology and Urology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, New York 14642, USA Chawnshang Chang Liver Cancer Center, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University, Hangzhou, China.
Endocr Relat Cancer. 2014 May 6;21(3):R165-82. doi: 10.1530/ERC-13-0283. Print 2014 Jun.
Androgen/androgen receptor (AR) signaling plays important roles in normal liver function and in progression of liver diseases. In studies of noncancerous liver diseases, AR knockout mouse models of liver disease have revealed that androgen/AR signaling suppresses the development of steatosis, virus-related hepatitis, and cirrhosis. In addition, studies have shown that targeting AR in bone marrow-derived mesenchymal stem cells (BM-MSCs) improves their self-renewal and migration potentials, thereby increasing the efficacy of BM-MSC transplantation as a way to control the progression of cirrhosis. Androgen/AR signaling is known to be involved in the initiation of carcinogen- or hepatitis B virus-related hepatocellular carcinoma (HCC). However, studies have demonstrated that AR, rather than androgen, plays the dominant role in cancer initiation. Therefore, targeting AR might be an appropriate therapy for patients with early-stage HCC. In contrast, androgen/AR signaling has been shown to suppress metastasis of HCC in patients with late-stage disease. In addition, there is evidence that therapy comprising Sorafenib and agents that enhance the functional expression of AR may suppress the progression of late-stage HCC.
雄激素/雄激素受体 (AR) 信号在正常肝脏功能和肝脏疾病的进展中发挥重要作用。在非癌症性肝脏疾病的研究中，AR 基因敲除小鼠肝脏疾病模型表明，雄激素/AR 信号抑制脂肪变性、病毒相关肝炎和肝硬化的发展。此外，研究表明，靶向骨髓间充质干细胞 (BM-MSCs) 中的 AR 可提高其自我更新和迁移潜能，从而提高 BM-MSC 移植作为控制肝硬化进展的疗效。雄激素/AR 信号参与致癌物或乙型肝炎病毒相关肝细胞癌 (HCC) 的启动。然而，研究表明，在癌症的启动阶段，AR 而不是雄激素发挥主导作用。因此，靶向 AR 可能是治疗早期 HCC 患者的一种合适方法。相反，雄激素/AR 信号已被证明可抑制晚期 HCC 患者的转移。此外，有证据表明，索拉非尼联合增强 AR 功能表达的药物治疗可能抑制晚期 HCC 的进展。
