Infection of HepG2 cells with recombinant adenovirus encoding the HCV core protein induces p21(WAF1) down-regulation -- effect of transforming growth factor beta.
J Hepatol
; 37(4): 486-92, 2002 Oct.
Article
em En
| MEDLINE
| ID: mdl-12217602
ABSTRACT
BACKGROUND/AIMS:
Chronic infection with hepatitis C virus leads to liver cirrhosis and hepatocellular carcinoma. Hepatocellular carcinoma is sometimes associated with p53 dysfunction and decreased p21(WAF1) expression. The p21(WAF1) gene is a major target of p53, and p21(WAF1) protein regulates the activities of cyclin/CDK complexes involved in cell cycle control and tumor formation. Because core protein has oncogenic properties, we investigated the expression of p21(WAF1) following core expression.METHODS:
We analyzed by Western blot, Northern blot and transfection the expression of p21(WAF1) in HepG2 cell line under transient expression of Hepatitis C core protein by recombinant-adenoviral infection. RESULTS ANDDISCUSSION:
Infection of HepG2 with core-encoding viruses induced the down-regulation of p21(WAF1) expression. This effect is due to a decrease in the p21(WAF1) gene transcription and of the p21(WAF1) protein half-life. These results support a role for Hepatitis C virus core protein in cell transformation. We also found also that the transforming growth factor beta can counteract the core-induced p21(WAF1) down-regulation. The antagonist effect of TGF beta, or of other molecules, on p21(WAF1) expression may be of particular interest for the treatment of HCV-positive hepatocellular carcinoma.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas do Core Viral
/
Fator de Crescimento Transformador beta
/
Ciclinas
/
Carcinoma Hepatocelular
/
Neoplasias Hepáticas
Limite:
Humans
Idioma:
En
Revista:
J Hepatol
Assunto da revista:
GASTROENTEROLOGIA
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
França