Loss of PTEN facilitates HIF-1-mediated gene expression

In glioblastoma-derived cell lines, PTEN does not significantly alter apopt otic sensitivity or cause complete inhibition of DNA synthesis. However, in these cell lines PTEN regulates hypoxia- and IGP-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 h ypoxia and IGF-1 induction of HIE-1-regulated genes. In addition, Akt activ ation leads to HIE-1 alpha stabilization, whereas PTEN attenuates hypoxia-m ediated HIF-1 alpha stabilization. We propose that loss of PTEN during mali gnant progression contributes to tumor expansion through the deregulation o f Akt activity and HIE-1-regulated gene expression.