國家衛生研究院 NHRI:Item 3990099045/6437
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    题名: Type II ground glass hepatocytes Co-express HBsAg and HBx proteins and represent preneoplastic lesions
    作者: Wu, HC;Hsieh, WC;Teng, CF;Wang, LHC;Tsai, HW;Yuan, Q;Zhang, J;Su, IJ
    贡献者: Division of Infectious Diseases
    摘要: Ground glass hepatocytes (GGHs) represent the hallmark of chronic HBV infection and harbor HBV pre-S mutants with deletions over the pre-S1 and pre-S2 regions in type I and type II GGHs, respectively. The mutant pre-S large surface proteins are accumulated in endoplasmic reticulum (ER) and induce ER stress, DNA damage, and genomic instability. Although HBx protein has been extensively studied as a HBV oncoprotein, very few studies clarify its exact location in the hepatocytes of clinical specimens. In this study, we investigated the expression of HBx using a recently developed monoclonal antibody speci?cally against HBx. We demonstrated that HBx was co-expressed with HBsAg in the Type II GGHs in 5 out of 20 HBsAg positive liver specimens. Type I GGHs, however, only inconsistently co-expressed HBsAg and HBx. Interestingly, HBx never expressed in hepatocytes alone but consistently co-expressed with HBsAg once expressed. In vitro, Huh7 cells over-expressed HBx and pre-S2 deletion mutants showed synergistic up-regulation of VEGF-A, pAKT1/2/3, pERK1/2 signals and p-mTOR signals. Human HCC tissues harboring pre-S2 mutants were also found to exhibit higher levels of p-mTOR as compared to wild type pre-S (p=0.0109). Furthermore, transgenic mice harboring double-constructs of HBx and pre-S2 mutant developed liver cancers in 13 months, far earlier than the HBx (16 months) or pre-S2 mutant (24 months) alone. We conclude that ground glass hepatocytes, especially type II GGHs, have co-expression of 2 HBV viral oncoproteins and represent precursor neoplastic lesions of HCC.
    日期: 2012-04
    關聯: Journal of Hepatology. 2012 Apr;56(Suppl. 2):S181.
    Link to: http://dx.doi.org/10.1016/S0168-8278(12)60470-X
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0168-8278&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000303241301017
    显示于类别:[蘇益仁(2002-2015)] 會議論文/會議摘要

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