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• W1976711675 abstract "Abstract Ionizing radiation induces an intracellular stress response via activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt survival pathway. In tumor cells, the PI3K/Akt pathway is induced through activation of members of ErbB receptor tyrosine kinases. Here, we investigated the receptor dependence of radiation-induced PI3K/Akt activation in tumor cells and in endothelial cells. The integrity of both the ErbB and the vascular endothelial growth factor (VEGF) ligand-activated PI3K/Akt pathway in endothelial cells was demonstrated using specific ErbB and VEGF receptor tyrosine kinase inhibitors. Irradiation of endothelial cells resulted in protein kinase B (PKB)/Akt activation in a similar time course as observed in response to VEGF. More importantly, radiation-induced PKB/Akt phosphorylation in endothelial cells was strongly down-regulated by the VEGF receptor tyrosine kinase inhibitor, whereas the ErbB receptor tyrosine kinase inhibitor did not affect PKB/Akt stimulation in response to irradiation. An opposite receptor dependence for radiation-induced PKB/Akt phosphorylation was observed in ErbB receptor-overexpressing A431 tumor cells. Furthermore, direct VEGF receptor phosphorylation was detected after irradiation in endothelial cells in absence of VEGF, which was almost completely inhibited after irradiation in presence of the VEGF receptor tyrosine kinase inhibitor. These data demonstrate that ionizing radiation induces VEGF ligand-independent but VEGF receptor-dependent PKB/Akt activation in endothelial cells and that PI3K/Akt pathway activation by radiation occurs in a differential cell type and receptor-dependent pattern." @default.
• W1976711675 created "2016-06-24" @default.
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• W1976711675 date "2004-08-01" @default.
• W1976711675 modified "2023-10-18" @default.
• W1976711675 title "Differential Activation of the Phosphatidylinositol 3′-Kinase/Akt Survival Pathway by Ionizing Radiation in Tumor and Primary Endothelial Cells" @default.
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• W1976711675 doi "https://doi.org/10.1158/0008-5472.can-03-3369" @default.
• W1976711675 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/15289348" @default.
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