國家衛生研究院 NHRI:Item 3990099045/2076

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/2076

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Title:	Hepatitis B virus pre-S mutants, endoplasmic reticulum stress and hepatocarcinogenesis
Authors:	Wang, HC;Huang, WY;Lai, MD;Su, IJ
Contributors:	Division of Clinical Research
Abstract:	Although hepatitis B virus (HBV) has been documented to cause hepatocellular carcinoma (HCC), the exact role of HBV in the development of HCC remains enigmatic. Several hypotheses have been proposed to explain the potential mechanism, including insertional mutagenesis of HBV genomes and transcriptional activators of HBV gene products such as hepatitis B x protein (HBx) and truncated middle S mutants. In the past few years, we have identified two types of large HBV surface antigens (LHBs) with deletions at the pre-S1 (Delta S1-LHBs) and pre-S2 (Delta S2-LHBs) regions in ground glass hepatocytes. The pre-S mutant LHBs are retained in the endoplasmic reticulum (ER) and escape from immune attack. The pre-S mutants, particularly Delta S2-LHBs, are increasingly prevalent in patients with hepatitis B e antigen (HBeAg)-positive chronic HBV infection, ranging from 6% before the 3rd decade to 35% in the 6th decade. In HCC patients, the two pre-S mutants were detected in 60% of HCC patients, in the serum and in HCC tissues. Pre-S mutant LHBs can initiate ER stress to induce oxidative DNA damage and genomic instability. Furthermore, pre-S mutant LHBs can upregulate cyclooxygenase-2 and cyclin A to induce cell cycle progression and proliferation of hepatocytes. In transgenic mice, the pre-S mutants can induce dysplasia of hepatocytes and development of HCC. In a nested control study, the presence of pre-S mutants carried a high risk of developing HCC in HBV carriers. In summary, the findings we describe in this review suggest a potential role for HBV pre-S mutants in HBV-related hepatocarcinogenesis, providing a model of viral carcinogenesis associated with ER stress.
Keywords:	Oncology
Date:	2006-08
Relation:	Cancer Science. 2006 Aug;97(8):683-688.
Link to:	http://dx.doi.org/10.1111/j.1349-7006.2006.00235.x
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1347-9032&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000238743000001
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33745593035
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles

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