國家衛生研究院 NHRI:Item 3990099045/2100

NHRI > National Institute of Infectious Diseases and Vaccinology > Ih-Jen Su(2002-2015) > Periodical Articles > Item 3990099045/2100

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/2100

Title:	Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes
Authors:	Wang, HC;Chang, WT;Chang, WW;Wu, HC;Huang, WY;Lei, HY;Lai, MD;Fausto, N;Su, IJ
Contributors:	Division of Clinical Research
Abstract:	Naturally occurring mutants with a deletion in the pre-S2 region of the large surface protein (Delta S2-LHBs) are prevalent in serum and livers of patients with chronic hepatitis B virus (HBV) infection associated with cirrhosis. The Delta S2-LHBs protein is retained in the endoplasmic reticulum (ER) and may induce ER stress. One interesting observation is the consistently clustered distribution of hepatocytes expressing Delta S2-LHBs. In this study, complementary DNA microarray analysis identified cyclin A and several groups of genes as being significantly upregulated by Delta S2-LHBs in the HuH-7 cell line. This observation was confirmed in liver tissues. The induction of cyclin A expression may occur via the specific transactivator function of Delta S2-LHBs independent of ER stress. In the presence of Delta S2-LHBs, hepatocytes sustained cyclin A expression and cell cycle progression under ER stress and displayed increased BrdU incorporation with multinuclear formation. Furthermore, Delta S2-LHBs could enhance anchorage-independent cell growth in a nontransformed human hepatocyte line and induced nodular proliferation of hepatocytes in transgenic mice. In conclusion, these in vitro and in vivo data support a role for Delta S2-LHBs in the hepatocyte hyperplasia and a likely role in the process of HBV-related tumorigenesis.
Keywords:	Gastroenterology & Hepatology
Date:	2005-04
Relation:	Hepatology. 2005 Apr;41(4):761-770.
Link to:	http://dx.doi.org/10.1002/hep.20615
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0270-9139&DestApp=IC2JCR
Cited Times(WOS):	https://www.webofscience.com/wos/woscc/full-record/WOS:000228006000012
Cited Times(Scopus):	http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=16244375544
Appears in Collections:	[Ih-Jen Su(2002-2015)] Periodical Articles

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