Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.

作者: Peter Carmeliet , Yuval Dor , Jean-Marc Herbert , Dai Fukumura , Koen Brusselmans

DOI: 10.1038/28867

关键词:

摘要: As a result of deprivation oxygen (hypoxia) and nutrients, the growth viability cells is reduced. Hypoxia-inducible factor (HIF)-1alpha helps to restore homeostasis by inducing glycolysis, erythropoiesis angiogenesis. Here we show that hypoxia hypoglycaemia reduce proliferation increase apoptosis in wild-type (HIF-1alpha+/+) embryonic stem (ES) cells, but not ES with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, deficiency does affect induced cytokines. We find hypoxia/hypoglycaemia-regulated involved controlling cell cycle are either HIF-1alpha-dependent (those encoding proteins p53, p21, Bcl-2) or HIF-1alpha-independent (p27, GADD153), suggesting there at least two different adaptive responses being deprived nutrients. Loss reduces hypoxia-induced expression vascular endothelial factor, prevents formation large vessels ES-derived tumours, impairs function, resulting hypoxic microenvironments within tumour mass. However, tumours was retarded accelerated, owing decreased increased stress-induced proliferation. stress contributes many (patho)biological disorders, this new role for control death may be general pathophysiological importance.

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