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- Title
Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice.
- Authors
Rankin, Erinn B; Rha, Jennifer; Unger, Travis L; Wu, Chia H; Shutt, Heather P; Johnson, Randall S; Simon, M Celeste; Keith, Brian; Haase, Volker H
- Abstract
The von Hippel-Lindau tumor suppressor pVHL regulates the stability of hypoxia-inducible factors (HIF)-1 and -2, oxygen-sensitive basic helix-loop-helix transcription factors, which mediate the hypoxic induction of angiogenic growth factors such as vascular endothelial growth factor. Loss of pVHL function results in constitutive activation of HIF-1 and HIF-2 and is associated with the development of highly vascularized tumors in multiple organs. We have used a conditional gene-targeting approach to investigate the relative contributions of HIF-1 and HIF-2 to VHL-associated vascular tumorigenesis in a mouse model of liver hemangiomas. Here we demonstrate genetically that conditional inactivation of HIF-2alpha suppressed the development of VHL-associated liver hemangiomas and that angiogenic gene expression in hepatocytes is predominantly regulated by HIF-2 and not by HIF-1. These findings suggest that HIF-2 is the dominant HIF in the pathogenesis of VHL-associated vascular tumors and that pharmacologic targeting of HIF-2 may be an effective strategy for their treatment.
- Publication
Oncogene, 2008, Vol 27, Issue 40, p5354
- ISSN
1476-5594
- Publication type
Journal Article
- DOI
10.1038/onc.2008.160