性激素在引起与乙型肝炎有关的肝癌中扮演着一个角色，这可能有助于解开一个几十年之久的谜团，即为什么罹患乙肝的男性会比女性更容易得肝癌。
这些发现表明，用药物来破坏肿瘤的雄激素受体可能是与早期肝癌较量的一种新的方法。 肝脏是人体内最大的内脏，而肝癌是排第五的最常见癌症，它也是全球癌症死亡中排第三位的癌症。 乙型肝炎感染（它在许多亚洲国家中流行，其中包括中国）与肝癌的关系是独特的，乙型肝炎肝癌占了全球肝癌 病例中的大约一半。
现在，Ming-Heng Wu及其同僚发现了为什么罹患乙型肝炎的男性要比女性更容易发展成为肝癌，这一答案深埋在该病毒的基因组中。该病毒的基因组中含有一个特别的可特异性地吸引雄性激素受体的DNA片断。肝细胞中的雄激素受体可与该片断结合并激发出对肝组织的一连串的损害。研究人员发现，通过将雄激素受体作为标靶（而不是将雄激素作为标靶），他们能够明显地抑制小鼠中的癌症生长。在该实验中，他们第一次用乙型肝炎病毒制造出了基因改变的小鼠，这些小鼠可在接触低剂量的某致癌物时产生肝肿瘤。
Wu及其同僚接着显示，雄激素受体可被一种化合物摧毁，并从而抑制了肝肿瘤的生长。 该治疗不会改变身体中总体雄激素的水平，而且在小鼠中没有明显的毒性效应；这些都提示，以雄激素受体作为标靶而不是以雄激素作为标靶的药物可能是治疗肝癌的一种有前途的疗法。 （生物谷Bioon.com）
关于肝炎肝癌的更多阅读
Nature Cell Biology：microRNA分子miR-151与肝癌转移
Hepatology：酪氨酸受体激酶EphrinA2可促进肝癌生长和转移
NEJM：microRNA表达影响肝癌复发
PNAS：阐明酗酒及丙肝引发肝癌机制
JAMA：原发性肝癌治疗新方法
生物谷推荐原文出处：
Science TM DOI: 10.1126/scitranslmed.3001143
Androgen Receptor Promotes Hepatitis B Virus–Induced Hepatocarcinogenesis Through Modulation of Hepatitis B Virus RNA Transcription
Ming-Heng Wu1,2,*, Wen-Lung Ma2,3,*, Cheng-Lung Hsu2,4,*, Yuh-Ling Chen1,2, Jing-Hsiung James Ou5, Charlotte Kathryn Ryan2, Yao-Ching Hung3, Shuyuan Yeh2 and Chawnshang Chang2,3,?
1Institute of Basic Medical Sciences, National Cheng Kung University, Tainan 701, Taiwan.
2George Whipple Lab for Cancer Research, Departments of Pathology and Urology and Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
3Sex Hormone Research Center, Graduate Institute of Clinical Medical Science, Department of Obstetrics and Gynecology, China Medical University/Hospital, Taichung 404, Taiwan.
4Division of Hematology-Oncology, Department of Internal Medicine, Chang Gung University/Memorial Hospital, Taoyuan 33305, Taiwan.
5Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA 90089, USA.
Hepatitis B virus (HBV)–induced hepatitis and carcinogen-induced hepatocellular carcinoma (HCC) are associated with serum androgen concentration. However, how androgen or the androgen receptor (AR) contributes to HBV-induced hepatocarcinogenesis remains unclear. We found that hepatic AR promotes HBV-induced hepatocarcinogenesis in HBV transgenic mice that lack AR only in the liver hepatocytes (HBV-L-AR?/y). HBV-L-AR?/y mice that received a low dose of the carcinogen N′-N′-diethylnitrosamine (DEN) have a lower incidence of HCC and present with smaller tumor sizes, fewer foci formations, and less α-fetoprotein HCC marker than do their wild-type HBV-AR+/y littermates. We found that hepatic AR increases the HBV viral titer by enhancing HBV RNA transcription through direct binding to the androgen response element near the viral core promoter. This activity forms a positive feedback mechanism with cooperation with its downstream target gene HBx protein to promote hepatocarcinogenesis. Administration of a chemical compound that selectively degrades AR, ASC-J9, was able to suppress HCC tumor size in DEN-HBV-AR+/y mice. These results demonstrate that targeting the AR, rather than the androgen, could be developed as a new therapy to battle HBV-induced HCC.
