中国科技核心期刊
CN:31-1600/Q
ISSN:1004-0374
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《生命科学》 2016, 28(11): 1321-1327
雄激素受体在肝细胞肝癌中作用的研究进展
盛 宇1,王春玉2,赵 越2*
(1 中国医科大学七年制,沈阳 110122;2 中国医科大学基础医学院卫生部细胞生物学
    重点实验室,教育部医学细胞生物学重点实验室,染色质生物学研究室,沈阳 110122)
摘 要:雄激素受体(androgen receptor, AR) 是核受体超家族中的成员,主要以雄激素依赖的方式诱导下游靶基因转录。在此过程中,AR 招募辅调节因子参与调控下游靶基因转录,从而发挥其生物学功能。近年研究证实,AR 在肝细胞肝癌(hepatocellular carcinoma, HCC) 发生发展中发挥重要作用。一方面,AR 介导的下游靶基因(TGF-β1、VEGF、CCRK 等) 的异常表达影响HCC 细胞的生长、增殖、血管形成等进程。乙肝病毒HBV X 蛋白通过激活c-Src 激酶等途径上调AR 的转录活性,从而促进HCC 的发展。另一方面,还有研究证实,AR 可抑制HCC 细胞的转移。现主要综述AR 介导的基因转录调控在HCC 中作用的分子机制,这将为HCC 的早期发现及治疗提供理论依据和新的思路。
 
Androgen receptor-mediated transactivation in hepatocellular carcinoma
SHENG Yu1, WANG Chun-Yu2, ZHAO Yue2*
(1 Seven-year Postgraduate, China Medical University, Shenyang 110122, China; 2 Laboratory of Chromatin Biology, Department of Cell Biology, Key Laboratory of Public Health of China, Department of Medical Cell Biology of Ministry of Education, China Medical University, Shenyang 110122, China)
Abstract: Androgen receptor (AR) is a member of the nuclear receptor superfamily. AR induces its target gene transcription in a ligand-depend manner. In this process, the co-regulators are recruited to modulate AR-induced transactivation. Thus, AR exerts its biological functions through the activation of its target genes. Recently,researches have indicated that AR plays a crucial role in the development of hepatocellular carcinoma (HCC). On one hand, abnormal expression of AR target genes, including TGF-β1, VEGF and CCRK influences cell growth, proliferation, or vascularization in HCC. HBV X protein upregulates AR-mediated transactivation by activating c-Src kinase pathway to stimulate HCC development. On the other hand, AR has been demonstrated to be also involved in the inhibition of HCC metastasis. In this review, we describe the molecular mechanisms and roles of AR-induced transactivation in HCC progression and development, which would provide novel ideas and targets for early detection and treatment of HCC.
 
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