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Phosphoinositide 3 kinase is critical for survival, mitogenesis and migration but not for differentiation of endothelial cells

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Abstract

Angiogenesis involves endothelial cell invasion and migration into the surrounding tissue where cells differentiate, to form new lumen-containing vessels. We have investigated the role of phosphoinositide 3-kinase (PI3-kinase) in vascular endothelial growth factor (VEGF)- and fibroblast growth factor (FGF)-induced angiogenesis. Angiogenesis in vivo in chick embryos was inhibited by treatment with the PI3-kinase inhibitors wortmannin and LY294002. Stimulation of primary bovine capillary endothelial (BCE) cells with FGF-2, VEGF-A165, or a combination of the two induced PI3-kinase activity in vitro and subsequent activation of the serine/threonine kinase Akt. The combination of FGF-2 and VEGF-A165 led to an additive response. Activation of PI3-kinase was strictly required for FGF-2- and VEGF-A165-induced migration and DNA synthesis of BCE cells. Tubular morphogenesis was unaffected by treatment with wortmannin or LY294002, but survival of the tubular structures was dependent on PI3-kinase activity. VEGF-A165 and FGF-2 induced increased stability of the tubular structures in a synergistic manner. These data indicate that PI3-kinase activity is required for migration, mitogenicity and survival but not for differentiation of endothelial cells during angiogenesis.

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Qi, JH., Matsumoto, T., Huang, K. et al. Phosphoinositide 3 kinase is critical for survival, mitogenesis and migration but not for differentiation of endothelial cells. Angiogenesis 3, 371–380 (1999). https://doi.org/10.1023/A:1026565908445

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