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Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas.

Authors
Type
Published Article
Journal
Frontiers of medicine in China
Publication Date
Volume
4
Issue
4
Pages
399–411
Identifiers
DOI: 10.1007/s11684-010-0170-y
PMID: 21107751
Source
Medline
License
Unknown

Abstract

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 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-type β-catenin expression and enforcing β-catenin-dependent signaling pathway, thus inducing cellular changes leading to acquisition of metastatic and/or proliferation properties.

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