HBx triggers either cellular senescence or cell proliferation depending on cellular phenotype.
J Viral Hepat
; 23(2): 130-8, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26316075
ABSTRACT
Replicative senescence is a hallmark of chronic liver diseases including chronic hepatitis B virus (HBV) infection, whereas HBV-encoded oncoproteins HBx and preS2 have been found to overcome senescence. HBx possesses a C-terminal truncation mainly in hepatocellular carcinomas but also in noncancerous liver tissues. Here, by cell counting, BrdU incorporation, MTT proliferation assay, cell cycle analysis, SA-ßgal staining and Western blotting in primary and malignant cells, we investigated the effect of HBx C-terminal mutants on cellular senescence. HBx C-terminal mutants were found to trigger cellular senescence in primary MRC5 cells, and malignant liver cells Huh7, and SK-Hep1. In contrast, these mutants promoted the proliferation of HepG2 malignant liver cells. The pro-senescent effect of HBx relied on an increased p16(INK4a) and p21(Waf1/Cip1) expression, and a decreased phosphorylation of Rb. Together, these results suggest that the two main variants of HBx present in HBV-infected liver possess opposite effects on cellular senescence that depend on the phenotype of infected cells.
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MEDLINE
Assunto principal:
Precursores de Proteínas
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Transativadores
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Senescência Celular
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Proliferação de Células
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Antígenos de Superfície da Hepatite B
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Neoplasias Hepáticas
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article