Hepatitis C Virus Core Protein Induces Malignant Transformation Of Biliary Epithelial Cells By Activating Nuclear Factor-Kappa B Pathway
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY(2010)
Abstract
Background and Aim:In an earlier study, we found that hepatitis C virus core protein, HCV-C, participated in the malignant transformation of HCV-C transfected normal human biliary epithelial (hBE) cells by activating telomerase. Here we further investigated the signaling of the malignant transformation.Methods:Reverse transcription-polymerase chain reaction (RT-PCR), western blotting and immunoprecipitation were used to analyze the expression of HCV-C, human telomerase reverse transcriptase (hTERT), nuclear factor-kappa B (NF-kappa B) and NF-kappa B inhibitor alpha (I kappa B alpha) genes and the phosphorylation level of I kappa B alpha protein. Electrophoretic mobility shift assays (EMSA) and NF-kappa B-linked luciferase reporter assays were carried out to measure NF-kappa B activity.Results:The expression of HCV-C and hTERT was detected only in HCV-C-transfected hBE (hBE-HCV-C) cells but not in vector-transfected or parental hBE cells. More NF-kappa B protein accumulated in nuclear extracts of hBE-HCV-C cells rather than in those of control cells, though total NF-kappa B protein level showed no difference among these cells. DNA binding activity of NF-kappa B and the NF-kappa B-linked luciferase activity were much higher in HCV-C-transfected hBE cells than those in vector- or non-transfected hBE cells. In addition, the I kappa B alpha phosphorylation level, but not the I kappa B alpha mRNA or protein levels, was increased after HCV-C transfection.Conclusions:Hepatitis C virus core protein activates NF-kappa B pathway in hBE cells by increasing the phosphorylation of I kappa B alpha. The pathway may be responsible for HCV-C-induced malignant transformation of hBE cells.
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Key words
biliary tract neoplasms, hepatitis C virus core protein, nuclear factor-kappa B, nuclear factor-kappa B inhibitor alpha
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