Hepatitis B virus promotes hepatocarcinogenesis in... : Hepatology (original) (raw)
Original Articles
Zheng, Yanyan1; Chen, Wen-ling1; Louie, Stan G.2; Yen, Benedict T. S.3,4; Ou, Jing-hsiung James1*
1 Department of Molecular Microbiology and Immunology, University of Southern California, Los Angeles, CA
2 Department of Pharmacy, University of Southern California, Los Angeles, CA
3 Department of Pathology, University of California, San Francisco, CA
4 Pathology Services, Veterans Administration Medical Center, San Francisco, CA
*Address reprint requests to: Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, 2011 Zonal Avenue, HMR-401, Los Angeles, CA 90033
Email:[email protected]
Received 1 August 2006; Accepted 2 October 2006
Published online in Wiley InterScience (www.interscience.wiley.com).
Grant sponsor: National Institutes of Health; Grant Numbers: R21RR027812 R01CA055578 P30DK026743.
Potential conflict of interest: Nothing to report.
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Abstract
HBV is a major risk factor for hepatocellular carcinoma (HCC). However, whether HBV can directly cause HCC or only indirectly via the induction of chronic liver inflammation has been controversial. By using transgenic mice carrying the entire HBV genome as a model, we now demonstrate that HBV by itself is an inefficient carcinogen. However, it can efficiently promote hepatocarcinogenesis initiated by the carcinogen diethylnitrosamine (DEN). This effect of HBV does not involve chronic liver inflammation, is apparently due to enhanced hepatocellular apoptosis and compensatory regeneration following DEN treatment, and does not require the HBV X protein. Conclusion : Our results demonstrate a direct role of HBV in a hepatocarcinogenesis pathway that involves the interaction between this virus and a dietary carcinogen. (Hepatology 2007;45:16–21.)
Abbreviations: ADV, adefovir dipivoxil; ALT, alanine aminotransferase; BrdU, bromodeoxyuridine; DEN, diethylnitrosamine; HBx, HBV X protein; HCC, hepatocellular carcinoma.
Copyright © 2007 American Association for the Study of Liver Diseases.