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Genetic evidence for a tumor suppressor role of HIF-2α
- Source :
-
Cancer Cell . Aug2005, Vol. 8 Issue 2, p131-141. 11p. - Publication Year :
- 2005
-
Abstract
- Summary: The hypoxia-inducible transcription factors HIF-1α and HIF-2α 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-1α, while the role of HIF-2α remains largely unknown. Here, we show that overexpression of HIF-2α in rat glioma tumors enhances angiogenesis but reduces growth of these tumors, in part by increasing tumor cell apoptosis. Moreover, siRNA knockdown of HIF-2α 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-2α 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. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 15356108
- Volume :
- 8
- Issue :
- 2
- Database :
- Academic Search Index
- Journal :
- Cancer Cell
- Publication Type :
- Academic Journal
- Accession number :
- 18194120
- Full Text :
- https://doi.org/10.1016/j.ccr.2005.07.003