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PMID: 10691731 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Loss of PTEN facilitates HIF-1-mediated gene expression.

Genes & development ·Vol. 14 ·No. 4 ·2000-02-15 ·Pages 391-6

Zundel W, Schindler C, Haas-Kogan D, Koong A, Kaper F, Chen E, Gottschalk AR, Ryan HE, Johnson RS, Jefferson AB, Stokoe D, Giaccia AJ

Abstract

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.

MeSH Terms
Apoptosis Brain Neoplasms/genetics,pathology Cell Hypoxia/genetics Culture Media, Serum-Free/pharmacology Cyclooxygenase 1 DNA-Binding Proteins/physiology Disease Progression Endothelial Growth Factors/biosynthesis,genetics Gene Deletion Gene Expression Regulation, Neoplastic/genetics Genetic Complementation Test Glioblastoma/genetics,pathology Humans Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Insulin-Like Growth Factor I/pharmacology Isoenzymes/biosynthesis,genetics Lymphokines/biosynthesis,genetics Membrane Proteins Neoplasm Proteins/biosynthesis,genetics,physiology Nuclear Proteins/physiology PTEN Phosphohydrolase Phosphofructokinase-1/biosynthesis,genetics Phosphoric Monoester Hydrolases/deficiency,genetics,physiology Phosphotransferases (Alcohol Group Acceptor)/biosynthesis,genetics Prostaglandin-Endoperoxide Synthases/biosynthesis,genetics Protein Serine-Threonine Kinases Proto-Oncogene Proteins/physiology Proto-Oncogene Proteins c-akt Recombinant Fusion Proteins/physiology Transcription Factors Transfection Tumor Cells, Cultured Tumor Suppressor Proteins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors
Chemicals
Culture Media, Serum-Free DNA-Binding Proteins Endothelial Growth Factors HIF1A protein, human Hypoxia-Inducible Factor 1 Hypoxia-Inducible Factor 1, alpha Subunit Isoenzymes Lymphokines Membrane Proteins Neoplasm Proteins Nuclear Proteins Proto-Oncogene Proteins Recombinant Fusion Proteins Transcription Factors Tumor Suppressor Proteins Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors Insulin-Like Growth Factor I Cyclooxygenase 1 PTGS1 protein, human Prostaglandin-Endoperoxide Synthases Phosphotransferases (Alcohol Group Acceptor) phosphoglucokinase Phosphofructokinase-1 AKT1 protein, human Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt Phosphoric Monoester Hydrolases PTEN Phosphohydrolase PTEN protein, human
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Zundel W
Mayer Cancer Biology Research Laboratory, Department of Radiation Oncology, Stanford University, Stanford, California 94305-5468 USA.
Schindler C
Haas-Kogan D
Koong A
Kaper F
Chen E
Gottschalk A R
Ryan H E
Johnson R S
Jefferson A B
Stokoe D
Giaccia A J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
Published
2000-02-15
Pages
391-6
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC316386
Subset
IM
Grants
NCI NIH HHS · T32 CA009302 · United States
NCI NIH HHS · CA-73832 · United States
NCI NIH HHS · P01 CA067166 · United States
NCI NIH HHS · CA-67166 · United States
NCI NIH HHS · CA-09302 · United States
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PubMed source PMC Full Text View journal details
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