Document Detail

Human hepatitis B virus X protein is a possible mediator of hypoxia-induced angiogenesis in hepatocarcinogenesis.
MedLine Citation:
PMID:  10679226     Owner:  NLM     Status:  MEDLINE    
The hepatitis B virus (HBV)-encoded transcriptional activator HBV-X protein (HBx) was known to be involved in hepatocarcinogenesis. Hepatocarcinogenesis generally included an active angiogenesis that was mainly considered to be due to a local hypoxia in liver tissues. However, the exact mechanisms of HBx-induced hepatocarcinogenesis were poorly understood. In this study, we examined the role of HBx in the increased angiogenesis and the possible regulating mechanisms of HBx by hypoxia. We demonstrated that HBx stimulated the transcription of vascular endothelial growth factor (VEGF), a potent angiogenic factor, in HBx-stable transfectants. HBx-induced angiogenesis was confirmed by in vivo tumor angiogenesis assay, resulting in that the HBx transfectants increased the formation of new blood vessels compared to the control transfectants. Then, we demonstrated that the expression of HBx was enhanced after incubating HBV-infected hepatoma cells under hypoxia. Moreover, the activity of HBV enhancer 1 (Enh1) was increased when hepatoma cells transfected with the reporter plasmid containing HBV Enh1 were exposed to hypoxic conditions. These results strongly suggest that HBx may play a critical role in the hypoxia-induced angiogenesis through transcriptional activation of VEGF during hepatocarcinogenesis.
S W Lee; Y M Lee; S K Bae; S Murakami; Y Yun; K W Kim
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  268     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2000 Feb 
Date Detail:
Created Date:  2000-03-10     Completed Date:  2000-03-10     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  456-61     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Molecular Biology, Pusan National University, Pusan, 609-735, Korea.
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MeSH Terms
Cell Hypoxia
Cell Transformation, Neoplastic
Endothelial Growth Factors / biosynthesis,  genetics
Gene Expression Regulation, Viral
Hepatitis B virus / physiology*
Liver Neoplasms / blood supply*,  virology
Lymphokines / biosynthesis,  genetics
Neovascularization, Pathologic / virology*
Oxygen / physiology*
Trans-Activators / genetics,  physiology*
Tumor Cells, Cultured
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factors
Reg. No./Substance:
0/Endothelial Growth Factors; 0/Lymphokines; 0/Trans-Activators; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 0/hepatitis B virus X protein; 7782-44-7/Oxygen

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