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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2010, Vol. 4 Issue (4) : 399-411     DOI: 10.1007/s11684-010-0170-y
Research articles |
Dysregulation of β-catenin by hepatitis B virus X protein in HBV-infected human hepatocellular carcinomas
Lei CHEN1,Liang HU1,Liang LI1,Yuan LIU1,Qian-Qian TU1, Yan-Xin CHANG1,He-Xin YAN1,Meng-Chao WU2, Hong-Yang WANG3,
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;
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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.
Keywords hepatocellular carcinoma      hepatitis B virus X protein      β-catenin      cell adhesion      E-cadherin      transcriptional activation      
Issue Date: 05 December 2010
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