國家衛生研究院 NHRI:Item 3990099045/7842
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    題名: Ground-glass hepatocytes co-expressing hepatitis B virus X protein and surface antigens exhibit enhanced oncogenic effects and tumorigenesis
    作者: Wu, HC;Tsai, HW;Teng, CF;Hsieh, WC;Lin, YC;Wang, LHC;Yuan, Q;Su, IJ
    貢獻者: Division of Infectious Diseases
    摘要: Hepatitis B virus (HBV) X protein (HBx) and pre-S2 deletion mutant large surface antigens are oncoproteins that induce hepatocellular carcinoma (HCC). The interaction of these two oncoproteins in hepatocytes and its significance in tumorigenesis remain to be elucidated. In this study, we observed the co-expression of HBx with surface antigens in ground-glass hepatocytes in 5 of 20 hepatitis B surface antigen-positive livers. In vitro, hepatocytes co-expressing HBx and a pre-S2 mutant showed enhanced expression of vascular endothelial growth factor-A (VEGF-A), phosphorylated Akt1/2/3 (p-Akt1/2/3), phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2), and phosphorylated mammalian target of rapamycin (p-mTOR) signals. Transgenic mice harboring both HBx and pre-S2 mutant construct plasmids developed HCCs at an average of 15.1 months, earlier than animals carrying either HBx (16.9 months) or pre-S2 mutant (24.5 months) alone. The oncogenic signals of VEGF-A, p-Akt1/2/3, p-ERK1/2, and p-mTOR were sequentially and differentially activated at different stages in tumorigenesis. Phosphorylated mTOR was consistently activated in transgenic and human HCCs. We conclude that ground-glass hepatocytes co-expressing HBx and surface antigens exhibit enhanced oncogenic effects and tumorigenesis in chronic HBV infections. The mTOR signal cascade may be the key regulator in HBV tumorigenesis and may be useful targets in the design of HCC therapy.
    日期: 2014-06
    關聯: Human Pathology. 2014 Jun;45(6):1294-1301.
    Link to: http://dx.doi.org/10.1016/j.humpath.2013.10.039
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0046-8177&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000336640000022
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84901414896
    顯示於類別:[蘇益仁(2002-2015)] 期刊論文

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