Cell cycle perturbation in a human hepatoblastoma cell line constitutively expressing Hepatitis C virus core protein

Cell cycle perturbation in a human hepatoblastoma cell line constitutively expressing Hepatitis C... Hepatitis C virus (HCV) is one of the major causes of chronic liver disease with the potential for development of hepatocellular carcinoma (HCC). The core protein of HCV has been shown to modulate expression of various cellular genes and to influence a number of cellular functions. We investigated the effect of constitutively expressed HCV core protein on cell cycle progression in HepG2 cell line, which is derived from a differentiated human hepatoblastoma and shows biosynthetic features similar to human hepatocytes. The results indicated that stable expression of the core protein in unsynchronized HepG2 cells induced a perturbation of the cell cycle with reduced cell doubling meantime and increased S phase fraction. Increase of c-myc protein above the basal expression level was demonstrated with a significant increase of c-myc stability, as revealed by its prolonged intracellular half-life, in HepG2 expressing HCV core protein. In contrast, p53 and p21 levels were unchanged. These results suggest that HCV core protein may promote cell cycle progression in HepG2 cells possibly through increasing stability of c-myc oncoprotein. These results are in support of important role played by HCV core protein in virus-mediated pathogenesis in persistently infected hosts and in hepatocarcinogenesis. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Cell cycle perturbation in a human hepatoblastoma cell line constitutively expressing Hepatitis C virus core protein

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Publisher
Springer-Verlag
Copyright
Copyright © 2003 by Springer-Verlag/Wien
Subject
LifeSciences
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-003-0202-x
Publisher site
See Article on Publisher Site

Abstract

Hepatitis C virus (HCV) is one of the major causes of chronic liver disease with the potential for development of hepatocellular carcinoma (HCC). The core protein of HCV has been shown to modulate expression of various cellular genes and to influence a number of cellular functions. We investigated the effect of constitutively expressed HCV core protein on cell cycle progression in HepG2 cell line, which is derived from a differentiated human hepatoblastoma and shows biosynthetic features similar to human hepatocytes. The results indicated that stable expression of the core protein in unsynchronized HepG2 cells induced a perturbation of the cell cycle with reduced cell doubling meantime and increased S phase fraction. Increase of c-myc protein above the basal expression level was demonstrated with a significant increase of c-myc stability, as revealed by its prolonged intracellular half-life, in HepG2 expressing HCV core protein. In contrast, p53 and p21 levels were unchanged. These results suggest that HCV core protein may promote cell cycle progression in HepG2 cells possibly through increasing stability of c-myc oncoprotein. These results are in support of important role played by HCV core protein in virus-mediated pathogenesis in persistently infected hosts and in hepatocarcinogenesis.

Journal

Archives of VirologySpringer Journals

Published: Aug 1, 2003

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