【摘 要】
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Background Hepatitis B virus (HBV)-X protein(HBx) is a transactivator of host several cellular genes including alpha-fetoprotein(AFP) and AFP receptor(AFPR) which contributes to HBV-associated tumor d
【机 构】
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Hainan Provincial Key Laboratory of Carcinogenesis and Intervention,Hainan Medical College,Haikou 57
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Background Hepatitis B virus (HBV)-X protein(HBx) is a transactivator of host several cellular genes including alpha-fetoprotein(AFP) and AFP receptor(AFPR) which contributes to HBV-associated tumor development.The expression of AFP/AFPR are correlated with hepatocellular carcinoma(HCC)-initial cells.But the role of AFP and AFR in promoting occurrence of HBV-related HCC were still unclear.Methods A total of 71 clinical patients liver specimens, normal human liver cells L-02 and HCC cell lines, PLC/PRF/5 were selected for analyzing the effects of HBx on expression of AFP, AFPR and Src.The expression of goal proteins were detected by Immunohistochemical stained and Western blotting;HBx-expressed vectors were constructed and transfected into L-02 cells, laser confocal microscopy was applied to observe expression and location of AFP, AFPR and Src in the normal liver cells and HCC cells, soft agar colony formation assay was used to observe colonies formed of the cells.Results We confirmed HBx gives preference to promote the expression of AFP and AFPR;HBx priors to up-regulate the expression of AFPR and AFP in L-02 cells and in normal liver specimens;AFPR signal been able to stimulate Src expressed.The results also indicated that phosphatidylinositol 3-kinase(PI3K) inhibitors Ly294002 and GDC0941 effectively suppress AFPR mediated up-regulation expression of Src in AFPR positive HCC lines.Conclusions HBx priors to drive the expression of AFP and AFPR to promote expression of Src in normal liver cells and hepatoma cells;AFP and AFPR maybe play pivotal role in HBV-related hepatocarcinogenesis;Targeting AFPR is an available therapeutic strategy of HCC.
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Human cytoplasmic alpha-fetoprotein (AFP) has been classified as a member of the albuminoid gene family.The protein sequence of AFP has significant homology to that of human serum albumin (HAS), but t