Publications [#80086] of Christopher D. Kontos

Papers Published

1. J Huang, CD Kontos, PTEN modulates vascular endothelial growth factor-mediated signaling and angiogenic effects., The Journal of biological chemistry, vol. 277 no. 13 (March, 2002), pp. 10760-6, ISSN 0021-9258 [doi]
   (last updated on 2013/05/16)

   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.

   Keywords:
   Animals • Apoptosis • Cell Movement • Cells, Cultured • Endothelial Growth Factors • Endothelium, Vascular • Humans • Lymphokines • Male • Neovascularization, Physiologic • PTEN Phosphohydrolase • Phosphatidylinositol 3-Kinases • Phosphoric Monoester Hydrolases • Rats • Rats, Sprague-Dawley • Signal Transduction • Tumor Suppressor Proteins • Vascular Endothelial Growth Factor A • Vascular Endothelial Growth Factors • cytology • metabolism • physiology • physiology*