Research ArticleCancer

Androgen Receptor Promotes Hepatitis B Virus–Induced Hepatocarcinogenesis Through Modulation of Hepatitis B Virus RNA Transcription

Science Translational Medicine  19 May 2010:
Vol. 2, Issue 32, pp. 32ra35
DOI: 10.1126/scitranslmed.3001143

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Destroying the Source of Liver Cancer

Hepatocellular carcinoma represents the majority of cases of primary liver cancer; it is the fifth most common cancer and the third leading cause of cancer death worldwide. Several risk factors for hepatocellular carcinoma have been identified, but gender and hepatitis B virus (HBV) infection have proven to be uniquely associated with the disease by undetermined mechanisms. HBV infection alone, which is endemic in many Asian countries including China, accounts for approximately 53% of hepatocellular carcinoma cases worldwide. Decades of research have examined risk factor exposures such as age, history of hepatitis, occupation, regular alcohol drinking, regular cigarette smoking, and family history of liver cancer to explain the gender disparities that are so prevalent among HBV-induced liver cancers, but none of these were fully accountable, suggesting that other unknown susceptibilities are lurking.

Liver cancer arises most frequently in the setting of chronic liver inflammation. After infection by the hepatitis virus, the host’s inflammatory immune response to the viral antigens induces hepatocyte damage and is followed by the pathogenesis of liver cancer. Although it has been postulated that sex hormones may interact with HBV infection in the process and lead to a dominant sex disparity in liver cancer risk, this has never been decisively shown. Now, Wu et al. use a genetically modified mouse model of HBV-induced liver cancer to explore how sex hormones, and specifically their receptors, play a role in promoting the disease. They find that targeting of the androgen receptor—and not androgens, as is frequently done in the clinic—hampers tumor formation at the gross and mechanistic levels. These results shed new light on a previously unexplored pathway and provide an intervention modality that is translatable in the clinic, and may explain why men are more susceptible to liver cancer than women.

Footnotes

  • * These authors contributed equally to this work.

  • Citation: M.-H. Wu, W.-L. Ma, C.-L. Hsu, Y.-L. Chen, J.-H. James Ou, C. K. Ryan, Y.-C. Hung, S. Yeh, C. Chang, Androgen Receptor Promotes Hepatitis B Virus–Induced Hepatocarcinogenesis Through Modulation of Hepatitis B Virus RNA Transcription. Sci. Transl. Med. 2, 32ra35 (2010).