Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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-1alpha stabilization, whereas PTEN attenuates hypoxia-mediated HIF-1alpha stabilization. We propose that loss of PTEN during malignant progression contributes to tumor expansion through the deregulation of Akt activity and HIF-1-regulated gene expression.

Type

Journal article

Journal

Genes Dev

Publication Date

15/02/2000

Volume

14

Pages

391 - 396

Keywords

Apoptosis, Brain Neoplasms, Cell Hypoxia, Culture Media, Serum-Free, Cyclooxygenase 1, DNA-Binding Proteins, Disease Progression, Endothelial Growth Factors, Gene Deletion, Gene Expression Regulation, Neoplastic, Genetic Complementation Test, Glioblastoma, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Insulin-Like Growth Factor I, Isoenzymes, Lymphokines, Membrane Proteins, Neoplasm Proteins, Nuclear Proteins, PTEN Phosphohydrolase, Phosphofructokinase-1, Phosphoric Monoester Hydrolases, Phosphotransferases (Alcohol Group Acceptor), Prostaglandin-Endoperoxide Synthases, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins c-akt, Recombinant Fusion Proteins, Transcription Factors, Transfection, Tumor Cells, Cultured, Tumor Suppressor Proteins, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors