Loss of PTEN facilitates HIF-1-mediated gene expression
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In glioblastoma-derived cell lines, PTEN does not significantly alter apoptotic sensitivity or cause complete inhibition of DNA synthesis. However, in these cell lines PTEN regulates hypoxia- and IGF-1-induced angiogenic gene expression by regulating Akt activation of HIF-1 activity. Restoration of wild-type PTEN to glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. In addition, Akt activation leads to HIF-1α stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1α stabilization. We propose that loss ofPTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression.
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2013 ◽
Vol 756
(1-2)
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pp. 46-55
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2001 ◽
Vol 155
(7)
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pp. 1129-1136
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2020 ◽
Vol 146
(3)
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pp. 593-604
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1996 ◽
Vol 59
(6)
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pp. 916-924
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