The study investigates the role of PTEN in regulating hypoxia-induced gene expression and angiogenesis in glioblastoma cell lines. PTEN, a tumor suppressor gene, is often mutated in glioblastomas, and its loss is associated with tumor progression. The research shows that PTEN inactivation leads to the induction of hypoxia-inducible factor 1 (HIF-1)-regulated genes, such as VEGF and COX-1, through the activation of Akt. Wild-type PTEN expression in PTEN mutant cells blocks this activation, suggesting that PTEN negatively regulates HIF-1α stabilization and transcriptional activity. Additionally, PTEN does not significantly alter apoptotic sensitivity or DNA synthesis, but it attenuates hypoxia and IGF-1-induced angiogenic gene expression by regulating Akt activation. The findings indicate that PTEN loss contributes to tumor expansion by deregulating Akt activity and HIF-1-regulated gene expression, providing insights into the mechanisms of PTEN mutations in late-stage tumor development.The study investigates the role of PTEN in regulating hypoxia-induced gene expression and angiogenesis in glioblastoma cell lines. PTEN, a tumor suppressor gene, is often mutated in glioblastomas, and its loss is associated with tumor progression. The research shows that PTEN inactivation leads to the induction of hypoxia-inducible factor 1 (HIF-1)-regulated genes, such as VEGF and COX-1, through the activation of Akt. Wild-type PTEN expression in PTEN mutant cells blocks this activation, suggesting that PTEN negatively regulates HIF-1α stabilization and transcriptional activity. Additionally, PTEN does not significantly alter apoptotic sensitivity or DNA synthesis, but it attenuates hypoxia and IGF-1-induced angiogenic gene expression by regulating Akt activation. The findings indicate that PTEN loss contributes to tumor expansion by deregulating Akt activity and HIF-1-regulated gene expression, providing insights into the mechanisms of PTEN mutations in late-stage tumor development.