國家衛生研究院 NHRI:Item 3990099045/6208

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/6208

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Title:	Aberrant cyclin A expression and centrosome overduplication induced by hepatitis B virus Pre-S2 mutants and its implication in hepatocarcinogenesis
Authors:	Wang, LH;Huang, W;Lai, MD;Su, IJ
Contributors:	Division of Infectious Diseases
Abstract:	Ground glass hepatocytes harboring hepatitis B virus (HBV) pre-S2 mutants have been recognized as pre-neoplastic lesions of hepatocellular carcinoma (HCC). The pre-S2 mutants accumulated in endoplasmic reticulum (ER) can induce ER stress, upregulate cyclin A and promote hepatocyte proliferation. Notably, cyclin A was aberrantly detected in the cytoplasm, instead of nucleus, of pre-S2 mutant-transgenic mice livers, thereby raising the potential role of cytoplasmic cyclin A in HBV hepatocarcinogenesis. In this study, we confirmed that cyclin A was detected in the cytoplasm in the majority of HBV-related HCC tissues. In vitro, the pre-S2 mutant-initiated ER stress could induce cytoplasmic cyclin A mediated via cleavage by the calcium-dependent protease mu-calpain, resulting in an N-terminal truncated product which was preferentially located in the cytoplasm. The aberrant cyclin A expression subsequently induced centrosome overduplication, and this effect was abolished by calpain-specific inhibitors or RNA interference targeting to cyclin A. Overall, our data indicate that HBV pre-S2 mutant may elicit aberrant cyclin A expression and centrosome overduplication through ER stress induction and thereby represent a potential mechanism for the chromosome instability in HBV hepatocarcinogenesis.
Date:	2012-02
Relation:	Carcinogenesis. 2012 Feb;33(2):466-472.
Link to:	http://dx.doi.org/10.1093/carcin/bgr296
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0143-3334&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000300039800031
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84863076138
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles

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