Author/Authors :
Acker، نويسنده , , Till and Diez-Juan، نويسنده , , Antonio and Aragones، نويسنده , , Julian and Tjwa، نويسنده , , Marc and Brusselmans، نويسنده , , Koen and Moons، نويسنده , , Lieve and Fukumura، نويسنده , , Dai and Moreno-Murciano، نويسنده , , Maria Paz and Herbert، نويسنده , , Jean-Marc and Burger، نويسنده , , Angelika and Riedel، نويسنده , , Johanna and Elvert، نويسنده , , Gerd and Flamme، نويسنده , , Ingo and Maxwell، نويسنده , , Patrick H. and Collen، نويسنده , , Désiré and Dewerchin، نويسنده , , Mieke and Jain، نويسنده , , Rakesh K. and Plate، نويسنده , , Karl H. and Carmeliet، نويسنده , , Peter، نويسنده ,
Abstract :
Summary
poxia-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.
