國家衛生研究院 NHRI:Item 3990099045/2100
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    题名: Hepatitis B virus pre-S2 mutant upregulates cyclin A expression and induces nodular proliferation of hepatocytes
    作者: Wang, HC;Chang, WT;Chang, WW;Wu, HC;Huang, WY;Lei, HY;Lai, MD;Fausto, N;Su, IJ
    贡献者: Division of Clinical Research
    摘要: 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.
    关键词: Gastroenterology & Hepatology
    日期: 2005-04
    關聯: 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
    显示于类别:[蘇益仁(2002-2015)] 期刊論文

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