Loss of PTEN facilitates HIF-1-mediated gene expression. PTEN is a tumor suppressor gene that regulates the PI(3)K/Akt pathway, which is involved in cell survival, proliferation, and angiogenesis. In glioblastoma cells, PTEN loss leads to increased Akt activity, which stabilizes HIF-1α, a key regulator of hypoxia-induced gene expression. This results in enhanced expression of genes such as VEGF, which is critical for angiogenesis. PTEN also inhibits hypoxia-mediated HIF-1α stabilization, suggesting that PTEN loss contributes to tumor expansion by deregulating Akt activity and HIF-1-regulated gene expression. The study shows that PTEN restoration in glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. These findings highlight the role of PTEN in regulating hypoxia-inducible gene expression and suggest that PTEN mutations may contribute to tumor progression by promoting angiogenesis and resistance to apoptosis. The study also demonstrates that Akt activates HIF-1α, which in turn promotes the expression of genes involved in angiogenesis and cell survival. These results provide insights into the molecular mechanisms underlying the role of PTEN in tumor development and suggest that targeting PTEN or its downstream pathways could be a potential therapeutic strategy for glioblastoma.Loss of PTEN facilitates HIF-1-mediated gene expression. PTEN is a tumor suppressor gene that regulates the PI(3)K/Akt pathway, which is involved in cell survival, proliferation, and angiogenesis. In glioblastoma cells, PTEN loss leads to increased Akt activity, which stabilizes HIF-1α, a key regulator of hypoxia-induced gene expression. This results in enhanced expression of genes such as VEGF, which is critical for angiogenesis. PTEN also inhibits hypoxia-mediated HIF-1α stabilization, suggesting that PTEN loss contributes to tumor expansion by deregulating Akt activity and HIF-1-regulated gene expression. The study shows that PTEN restoration in glioblastoma cell lines lacking functional PTEN ablates hypoxia and IGF-1 induction of HIF-1-regulated genes. These findings highlight the role of PTEN in regulating hypoxia-inducible gene expression and suggest that PTEN mutations may contribute to tumor progression by promoting angiogenesis and resistance to apoptosis. The study also demonstrates that Akt activates HIF-1α, which in turn promotes the expression of genes involved in angiogenesis and cell survival. These results provide insights into the molecular mechanisms underlying the role of PTEN in tumor development and suggest that targeting PTEN or its downstream pathways could be a potential therapeutic strategy for glioblastoma.