Acker, T and Diez-Juan, A and Aragones, J and Tjwa, M and Brusselmans, K and Moons, L and Fukumura, D and Moreno-Murciano, MP and Herbert, JM and Burger, A and Riedel, J and Elverl, G and Flamme, I and Maxwell, PH and Collen, D and Dewerchin, M and Jain, RK and Plate, KH and Carmeliet, P (2005) Genetic evidence for a tumor suppressor role of HIF-2 alpha. CANCER CELL , 8 (2) 131 - 141. 10.1016/j.ccr.2005.07.003.
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The hypoxia-inducible transcription factors HIF-1 alpha and HIF-2 alpha are activated in hypoxic tumor regions. However, their role in tumorigenesis remains controversial, as tumor growth promoter and suppressor activities have been ascribed to HIF-1 alpha, while the role of HIF-2 alpha remains largely unknown. Here, we show that overexpression of HIF-2 alpha in rat glioma tumors enhances angiogenesis but reduces growth of these tumors, in part by increasing tumor cell apoptosis. Moreover, siRNA knockdown of HIF-2 alpha reduced apoptosis in hypoxic human malignant glioblastoma cells. Furthermore, inhibition of HIF by overexpression of a dominant-negative HIF transgene in glioma cells or HIF-2 alpha deficiency in teratomas reduced vascularization but accelerated growth of these tumor types. These findings urge careful consideration of using HIF inhibitors as cancer therapeutic strategies.
|Title:||Genetic evidence for a tumor suppressor role of HIF-2 alpha|
|Keywords:||HYPOXIA-INDUCIBLE FACTOR-1-ALPHA, ENDOTHELIAL GROWTH-FACTOR, RENAL-CELL CARCINOMA, RESPONSIVE TRANSCRIPTION FACTOR, PAS DOMAIN PROTEIN-1, FACTORS HIF-1-ALPHA, FACTOR 1-ALPHA, FACTOR-2-ALPHA HIF-2-ALPHA, FACTOR (HIF)-1-ALPHA, EMBRYOS LACKING|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of)|
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