| First Author | Rankin EB | Year | 2008 |
| Journal | Oncogene | Volume | 27 |
| Issue | 40 | Pages | 5354-8 |
| PubMed ID | 18490920 | Mgi Jnum | J:140075 |
| Mgi Id | MGI:3811705 | Doi | 10.1038/onc.2008.160 |
| Citation | Rankin EB, et al. (2008) Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice. Oncogene 27(40):5354-8 |
| abstractText | 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. |
