摘要
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.
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)
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).