Hepatitis B virus X protein induces angiogenesis by stabilizing hypoxia-inducible factor-1α

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Title
Hepatitis B virus X protein induces angiogenesis by stabilizing hypoxia-inducible factor-1α
Author(s)
E J Moon; C H Jeong; J W Jeong; K R Kim; Dae Yeul Yu; S Murakami; C W Kim; K W Kim
Bibliographic Citation
FASEB Journal, vol. 18, no. 2, pp. 382-384
Publication Year
2004
Abstract
Hepatitis B virus X protein (HBx) is closely involved in the development of hepatocellular carcinoma, a highly vascularized solid tumor. Here we show that HBx increases the transcriptional activity and protein level of hypoxia-inducible factor-1alpha (HIF-1alpha) under both normoxic and hypoxic conditions, and it also stimulates angiogenesis. HBx directly interacted with the bHLH/PAS domain of HIF-1alpha but not with the von Hippel-Lindau protein (pVHL). HBx decreased the binding of pVHL to HIF-1alpha and prevented ubiquitin-dependent degradation of HIF-1alpha. In HBx-transgenic mice, HIF-1alpha and vascular endothelial growth factor were strongly detected in the dysplastic lesion, where HBx was also more highly expressed than in the non-neoplastic region of the liver. An immunohistochemical study showed that microvessels are more abundant in the dysplastic lesion than in the non-neoplastic region. Our data suggest that HBx stabilizes HIF-1alpha and leads to angiogenesis during hepatocarcinogenesis.
ISSN
0892-6638
Publisher
Wiley
DOI
http://dx.doi.org/10.1096/fj.03-0153fje
Type
Article
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1. Journal Articles > Journal Articles
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