Back to Search
Start Over
PTEN Modulates Vascular Endothelial Growth Factor-Mediated Signaling and Angiogenic Effects
- Source :
- Journal of Biological Chemistry. 277:10760-10766
- Publication Year :
- 2002
- Publisher :
- Elsevier BV, 2002.
-
Abstract
- Phosphatidylinositol 3-kinase is activated by vascular endothelial growth factor (VEGF), and many of the angiogenic cellular responses of VEGF are regulated by the lipid products of phosphatidylinositol 3-kinase. The tumor suppressor PTEN has been shown to down-regulate phosphatidylinositol 3-kinase signaling, yet the effects of PTEN on VEGF-mediated signaling and angiogenesis are unknown. Inhibition of endogenous PTEN in cultured endothelial cells by adenovirus-mediated overexpression of a dominant negative PTEN mutant (PTEN-C/S) enhanced VEGF-mediated Akt phosphorylation, and this effect correlated with decreases in caspase-3 cleavage, caspase-3 activity, and DNA degradation after induction of apoptosis with tumor necrosis factor-alpha. Overexpression of PTEN-C/S also enhanced VEGF-mediated endothelial cell proliferation and migration. In contrast, overexpression of wild-type PTEN inhibited the anti-apoptotic, proliferative, and chemotactic effects of VEGF. Moreover, PTEN-C/S increased the length of vascular sprouts in the rat aortic ring assay and modulated VEGF-mediated tube formation in an in vitro angiogenesis assay, whereas PTEN-wild type inhibited these effects. Taken together, these findings demonstrate that PTEN potently modulates VEGF-mediated signaling and function and that PTEN is a viable target in therapeutic approaches to promote or inhibit angiogenesis.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
Angiogenesis
Neovascularization, Physiologic
Apoptosis
Endothelial Growth Factors
In Vitro Techniques
Biochemistry
Rats, Sprague-Dawley
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Cell Movement
Animals
Humans
PTEN
Phosphatidylinositol
Molecular Biology
Cells, Cultured
Tube formation
Lymphokines
biology
Vascular Endothelial Growth Factors
Tumor Suppressor Proteins
PTEN Phosphohydrolase
Cell Biology
Phosphoric Monoester Hydrolases
Rats
Cell biology
Vascular endothelial growth factor B
Endothelial stem cell
Vascular endothelial growth factor
chemistry
Cancer research
biology.protein
Tumor necrosis factor alpha
Endothelium, Vascular
Signal Transduction
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 277
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....da0b7d93cd045ab9878c02db1b695674