Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.
As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha helps to restore oxygen homeostasis by inducing glycolysis, erythropoiesis and angiogenesis. Here we show that hypoxia and hypoglycaemia reduce proliferat...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
1998
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| _version_ | 1797095070719016960 |
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| author | Carmeliet, P Dor, Y Herbert, J Fukumura, D Brusselmans, K Dewerchin, M Neeman, M Bono, F Abramovitch, R Maxwell, P Koch, C Ratcliffe, P Moons, L Jain, R Collen, D Keshert, E Keshet, E |
| author_facet | Carmeliet, P Dor, Y Herbert, J Fukumura, D Brusselmans, K Dewerchin, M Neeman, M Bono, F Abramovitch, R Maxwell, P Koch, C Ratcliffe, P Moons, L Jain, R Collen, D Keshert, E Keshet, E |
| author_sort | Carmeliet, P |
| collection | OXFORD |
| description | As a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha 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-1alpha+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, a deficiency of HIF-1alpha does not affect apoptosis induced by cytokines. We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1alpha-dependent (those encoding the proteins p53, p21, Bcl-2) or HIF-1alpha-independent (p27, GADD153), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients. Loss of HIF-1alpha 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-1alpha 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-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance. |
| first_indexed | 2024-03-07T04:22:48Z |
| format | Journal article |
| id | oxford-uuid:cb97b359-c37f-4af9-8e40-9f42182bd912 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:22:48Z |
| publishDate | 1998 |
| record_format | dspace |
| spelling | oxford-uuid:cb97b359-c37f-4af9-8e40-9f42182bd9122022-03-27T07:15:57ZRole of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:cb97b359-c37f-4af9-8e40-9f42182bd912EnglishSymplectic Elements at Oxford1998Carmeliet, PDor, YHerbert, JFukumura, DBrusselmans, KDewerchin, MNeeman, MBono, FAbramovitch, RMaxwell, PKoch, CRatcliffe, PMoons, LJain, RCollen, DKeshert, EKeshet, EAs a result of deprivation of oxygen (hypoxia) and nutrients, the growth and viability of cells is reduced. Hypoxia-inducible factor (HIF)-1alpha 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-1alpha+/+) embryonic stem (ES) cells, but not in ES cells with inactivated HIF-1alpha genes (HIF-1alpha-/-); however, a deficiency of HIF-1alpha does not affect apoptosis induced by cytokines. We find that hypoxia/hypoglycaemia-regulated genes involved in controlling the cell cycle are either HIF-1alpha-dependent (those encoding the proteins p53, p21, Bcl-2) or HIF-1alpha-independent (p27, GADD153), suggesting that there are at least two different adaptive responses to being deprived of oxygen and nutrients. Loss of HIF-1alpha 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-1alpha 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-1alpha in hypoxic control of cell growth and death may be of general pathophysiological importance. |
| spellingShingle | Carmeliet, P Dor, Y Herbert, J Fukumura, D Brusselmans, K Dewerchin, M Neeman, M Bono, F Abramovitch, R Maxwell, P Koch, C Ratcliffe, P Moons, L Jain, R Collen, D Keshert, E Keshet, E Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. |
| title | Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. |
| title_full | Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. |
| title_fullStr | Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. |
| title_full_unstemmed | Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. |
| title_short | Role of HIF-1alpha in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. |
| title_sort | role of hif 1alpha in hypoxia mediated apoptosis cell proliferation and tumour angiogenesis |
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