• DOI:10.1038/28867
• Corpus ID: 4419118

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

@article{Carmeliet1998RoleOH,
  title={Role of HIF-1$\alpha$ in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis},
  author={Peter Carmeliet and Yuval Dor and Jean-M. Herbert and Dai Fukumura and Koen Brusselmans and Mieke Dewerchin and Michal Neeman and Françoise Bono and Rinat Abramovitch and Patrick H. Maxwell and Cameron J. Koch and Peter J. Ratcliffe and Lieve Moons and Rakesh K. Jain and D{\'e}sir{\'e} Jos{\'e} Collen and Eli Keshet},
  journal={Nature},
  year={1998},
  volume={394},
  pages={485-490}
}

• P. Carmeliet, Y. Dor, +13 authors E. Keshet
• Published 30 July 1998
• Biology
• Nature

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