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

被引：15

作者：

Chen L. ^{[1
,2
]}

Hu L. ^{[1
,2
]}

Li L. ^{[1
,2
]}

Liu Y. ^{[1
,2
]}

Tu Q.-Q. ^{[1
,2
]}

Chang Y.-X. ^{[1
,2
]}

Yan H.-X. ^{[1
,2
]}

Wu M.-C. ^{[2
]}

Wang H.-Y. ^{[1
,2
,3
]}

机构：

[1] International Cooperation Laboratory on Signal Transduction, Eastern Hepatobiliary Surgery Institute, Second Military Medical University

[2] Second Military Medical University

[3] National Laboratory for Oncogenes and Related Genes, Key Lab of Cancer Institute in Renji Hospital, Shanghai Jiao-Tong University

来源：

Frontiers of Medicine in China | 2010年 / 4卷 / 4期

基金：

中国国家自然科学基金;

关键词：

β-catenin; cell adhesion; E-cadherin; hepatitis B virus X protein; hepatocellular carcinoma; transcriptional activation;

D O I：

10.1007/s11684-010-0170-y

中图分类号：

学科分类号：

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 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. © 2010 Higher Education Press and Springer-Verlag Berlin Heidelberg.

引用

页码：399 / 411

页数：12

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