Hypoxia-inducible factor-2 regulates vascular tumorigenesis in mice.

摘要: 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 hypoxic induction angiogenic growth such as vascular endothelial factor. Loss function results in constitutive activation HIF-1 HIF-2 is associated with development highly vascularized tumors multiple organs. We have used a conditional gene-targeting approach to investigate relative contributions VHL-associated tumorigenesis mouse model liver hemangiomas. Here we demonstrate genetically that inactivation HIF-2alpha suppressed hemangiomas gene expression hepatocytes predominantly regulated by not HIF-1. These findings suggest dominant HIF pathogenesis pharmacologic targeting may be an effective strategy for their treatment.