性激素在引起與乙型肝炎有關(guān)的肝癌中扮演著一個角色,，這可能有助于解開一個幾十年之久的謎團(tuán)，即為什么罹患乙肝的男性會比女性更容易得肝癌,。
這些發(fā)現(xiàn)表明，用藥物來破壞腫瘤的雄激素受體可能是與早期肝癌較量的一種新的方法,。 肝臟是人體內(nèi)最大的內(nèi)臟,，而肝癌是排第五的最常見癌癥，它也是全球癌癥死亡中排第三位的癌癥。 乙型肝炎感染（它在許多亞洲國家中流行,，其中包括中國）與肝癌的關(guān)系是獨(dú)特的,，乙型肝炎肝癌占了全球肝癌 病例中的大約一半。
現(xiàn)在,，Ming-Heng Wu及其同僚發(fā)現(xiàn)了為什么罹患乙型肝炎的男性要比女性更容易發(fā)展成為肝癌,，這一答案深埋在該病毒的基因組中。該病毒的基因組中含有一個特別的可特異性地吸引雄性激素受體的DNA片斷,。肝細(xì)胞中的雄激素受體可與該片斷結(jié)合并激發(fā)出對肝組織的一連串的損害,。研究人員發(fā)現(xiàn)，通過將雄激素受體作為標(biāo)靶（而不是將雄激素作為標(biāo)靶）,，他們能夠明顯地抑制小鼠中的癌癥生長,。在該實驗中，他們第一次用乙型肝炎病毒制造出了基因改變的小鼠,，這些小鼠可在接觸低劑量的某致癌物時產(chǎn)生肝腫瘤,。
Wu及其同僚接著顯示，雄激素受體可被一種化合物摧毀,，并從而抑制了肝腫瘤的生長,。 該治療不會改變身體中總體雄激素的水平，而且在小鼠中沒有明顯的毒性效應(yīng),；這些都提示,，以雄激素受體作為標(biāo)靶而不是以雄激素作為標(biāo)靶的藥物可能是治療肝癌的一種有前途的療法。 （生物谷Bioon.com）
關(guān)于肝炎肝癌的更多閱讀
Nature Cell Biology：microRNA分子miR-151與肝癌轉(zhuǎn)移
Hepatology：酪氨酸受體激酶EphrinA2可促進(jìn)肝癌生長和轉(zhuǎn)移
NEJM：microRNA表達(dá)影響肝癌復(fù)發(fā)
PNAS：闡明酗酒及丙肝引發(fā)肝癌機(jī)制
JAMA：原發(fā)性肝癌治療新方法
生物谷推薦原文出處：
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.
