Details

Autor(en) / Beteiligte

• RANKIN, E. B
• RHA, J
• UNGER, T. L
• WU, C. H
• SHUTT, H. P
• JOHNSON, R. S
• SIMON, M. C
• KEITH, B
• HAASE, V. H

Titel

Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice

Ist Teil von

• Oncogene, 2008-09, Vol.27 (40), p.5354-5358

Ort / Verlag

Basingstoke: Nature Publishing

Erscheinungsjahr

2008

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• 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.