Dysregulation of β-catenin by hepatitis
B virus X protein in HBV-infected human hepatocellular carcinomas
1.International Cooperation
Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute,
Second Military Medical University, Shanghai 200438, China; 2.Second Military Medical
University, Shanghai 200438, China; 3.International Cooperation
Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute,
Second Military Medical University, Shanghai 200438, China;National Laboratory
for Oncogenes and Related Genes, Key Lab of Cancer Institute in Renji
Hospital, Shanghai Jiao-Tong University, Shanghai 200441, China;
发布日期:
2010-12-05
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-type β-catenin and E-cadherin were decreased in HepG2 cells expressing hepatitis B virus X protein (HBx), accompanied by destabilization of adherens junction. Reverse transcriptase PCR (RT-PCR), Northern and Western blot showed that reduction of wild-type β-catenin expression involved degradation of the protein. However, RNA interference (RNAi) and luciferase assay indicated that HBx enhanced β-catenin mediated signaling in HepG2 cells. In addition, immunohistochemical and Western blot analysis of β-catenin revealed that a decrease in the β-catenin protein level was found in 58.3% of HBV-related HCCs 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-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.