β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway.In our study,we found that,in the development of hepatocellular carcinoma(HCC),β-catenin was correlated with hepatitis B viru...β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway.In our study,we found that,in the development of hepatocellular carcinoma(HCC),β-catenin was correlated with hepatitis B virus(HBV)X gene encoded protein,which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis.The expression levels of wild-typeβ-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein(HBx),accompanied by destabilization of adherens junction.Reverse transcrip-tase PCR(RT-PCR),Northern and Western blot showed that reduction of wild-typeβ-catenin expression involved degradation of the protein.However,RNA interference(RNAi)and luciferase assay indicated that HBx enhancedβ-catenin mediated signaling in HepG2 cells.In addition,immunohistochemical and Western blot analysis ofβ-catenin revealed that a decrease in theβ-catenin protein level was found in 58.3%of HBV-related HCCs versus 19.2%of non-HBV-related tumors.Our data suggest that the expression of HBx contributed to the development of HCC,in part,by repressing the wild-typeβ-catenin expression and enforcingβ-catenin-dependent signaling pathway,thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.展开更多
基金supported by the State Key Project for Liver Cancer(No.2008ZX10002)National High-Tech Research and Development Program of China(Nos.2006AA02A249,08Z20)+2 种基金National Science Fund for Distinguished Young Scholars(No.30921006)Key Program of National Natural Science Foundation of China(Grant No.90713032)the Science Foundation of Shanghai(Nos.10QA1408700 and 09CG33).
文摘β-catenin is a key molecule involved in both cell-cell adhesion and Wnt signaling pathway.In our study,we found that,in the development of hepatocellular carcinoma(HCC),β-catenin was correlated with hepatitis B virus(HBV)X gene encoded protein,which is essential for HBV infectivity and is a potential cofactor in viral carcinogenesis.The expression levels of wild-typeβ-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein(HBx),accompanied by destabilization of adherens junction.Reverse transcrip-tase PCR(RT-PCR),Northern and Western blot showed that reduction of wild-typeβ-catenin expression involved degradation of the protein.However,RNA interference(RNAi)and luciferase assay indicated that HBx enhancedβ-catenin mediated signaling in HepG2 cells.In addition,immunohistochemical and Western blot analysis ofβ-catenin revealed that a decrease in theβ-catenin protein level was found in 58.3%of HBV-related HCCs versus 19.2%of non-HBV-related tumors.Our data suggest that the expression of HBx contributed to the development of HCC,in part,by repressing the wild-typeβ-catenin expression and enforcingβ-catenin-dependent signaling pathway,thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.
