Title: Genetic evidence for a tumor suppressor role of HIF-2alpha
Authors: Acker, Till ×
Diez-Juan, Antonio
Aragones, Julian
Tjwa, Marc
Brusselmans, Koenraad
Moons, Lieve
Fukumura, Dai
Moreno-Murciano, Maria Paz
Herbert, Jean-Marc
Burger, Angelika
Riedel, Johanna
Elvert, Gerd
Flamme, Ingo
Maxwell, Patrick H
Collen, Desire
Dewerchin, Mieke
Jain, Rakesh K
Plate, Karl H
Carmeliet, Peter #
Issue Date: Aug-2005
Publisher: Cell Press
Series Title: Cancer Cell vol:8 issue:2 pages:131-41
Abstract: The hypoxia-inducible transcription factors HIF-1alpha and HIF-2alpha 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-1alpha, while the role of HIF-2alpha remains largely unknown. Here, we show that overexpression of HIF-2alpha in rat glioma tumors enhances angiogenesis but reduces growth of these tumors, in part by increasing tumor cell apoptosis. Moreover, siRNA knockdown of HIF-2alpha 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-2alpha 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.
ISSN: 1535-6108
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular and Vascular Biology
Animal Physiology and Neurobiology Section - miscellaneous
Vesalius Research Centre (-)
Clinical and Experimental Endocrinology
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
× corresponding author
# (joint) last author

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