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PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects.

Publication ,  Journal Article
Huang, J; Kontos, CD
Published in: J Biol Chem
March 29, 2002

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.

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Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 29, 2002

Volume

277

Issue

13

Start / End Page

10760 / 10766

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Tumor Suppressor Proteins
  • Signal Transduction
  • Rats, Sprague-Dawley
  • Rats
  • Phosphoric Monoester Hydrolases
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
  • Neovascularization, Physiologic
 

Citation

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Huang, J., & Kontos, C. D. (2002). PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. J Biol Chem, 277(13), 10760–10766. https://doi.org/10.1074/jbc.M110219200
Huang, Jianhua, and Christopher D. Kontos. “PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects.J Biol Chem 277, no. 13 (March 29, 2002): 10760–66. https://doi.org/10.1074/jbc.M110219200.
Huang J, Kontos CD. PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. J Biol Chem. 2002 Mar 29;277(13):10760–6.
Huang, Jianhua, and Christopher D. Kontos. “PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects.J Biol Chem, vol. 277, no. 13, Mar. 2002, pp. 10760–66. Pubmed, doi:10.1074/jbc.M110219200.
Huang J, Kontos CD. PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects. J Biol Chem. 2002 Mar 29;277(13):10760–10766.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

March 29, 2002

Volume

277

Issue

13

Start / End Page

10760 / 10766

Location

United States

Related Subject Headings

  • Vascular Endothelial Growth Factors
  • Vascular Endothelial Growth Factor A
  • Tumor Suppressor Proteins
  • Signal Transduction
  • Rats, Sprague-Dawley
  • Rats
  • Phosphoric Monoester Hydrolases
  • Phosphatidylinositol 3-Kinases
  • PTEN Phosphohydrolase
  • Neovascularization, Physiologic