Angiopoietin-2 at high concentration can enhance endothelial cell survival through the phosphatidylinositol 3'-kinase/Akt signal transduction pathway

• Published in: Oncogene Vol. 19; no. 39; pp. 4549 - 4552
• Main Authors: KIM, Injune, KIM, Ji-Hye, MOON, Sang-Ok, HEE JIN KWAK, KIM, Nam-Gyun, GOU YOUNG KOH
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing 14.09.2000; Nature Publishing Group
• Subjects: AKT protein; Androstadienes - pharmacology; Angiogenesis; Angiopoietin; Angiopoietin-2; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Cell activation; Cell Line; Cell physiology; Cell survival; Cell Survival - drug effects; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Chromones - pharmacology; Culture Media, Serum-Free - pharmacology; Dose-Response Relationship, Drug; Endothelial cells; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - metabolism; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Humans; Kinases; Microscopy; Molecular and cellular biology; Morpholines - pharmacology; mRNA; Neoplasm Proteins - metabolism; Neoplasm Proteins - pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phosphatidylinositol 3-Kinases - drug effects; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation; Protein-Serine-Threonine Kinases; Protein-serine/threonine kinase; Proteins - pharmacology; Proto-Oncogene Proteins - drug effects; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt; Receptor, TIE-2; Signal Transduction; Survival factor; Tumorigenesis; Umbilical vein; Umbilical Veins - cytology; Vascular endothelial growth factor; Wortmannin; Human; Angiogenesis; Signal transduction; Endothelial cell; Enzyme; Protein kinase; Transferases; C-Onc gene; Carcinogenesis; Survival; 1-Phosphatidylinositol 3-kinase; Apoptosis
• ISSN: 0950-9232; 1476-5594
• DOI: 10.1038/sj.onc.1203800

The angiopoietin-Tie2 system in endothelial cells is an important regulator of vasculogenesis and vascular integrity. High levels of angiopoietin-2 (Ang2) mRNA are observed in vascular activation during tumorigenesis. Although Ang2 is known to be a naturally occurring antagonist of angiopoietin-1 (Ang1) in vivo, the exact function of Ang2 itself is not known. Here, we found that a high concentration of Ang2 (800 ng/ml) acts as an apoptosis survival factor for endothelial cells during serum deprivation apoptosis. The survival effect of high concentration Ang2 was blocked by pre-treatment with soluble Tie2 receptor and the PI 3'-kinase-specific inhibitors, wortmannin and LY294002. Accordingly, 800 ng/ml of Ang2 induced phosphorylation of Tie2, the p85 subunit of phosphatidylinositol 3'-kinase (PI 3'-kinase), and serine-threonine kinase Akt at Ser473 in the human umbilical vein endothelial cells; lower concentrations of Ang2 (50 - 400 ng/ml) did not produce notable effects. These findings indicate that at high concentrations, Ang2, like Ang1, can be an apoptosis survival factor for endothelial cells through the activation of the Tie2 receptor, PI 3'-kinase and Akt, and thus may be a positive regulator of tumor angiogenesis. Oncogene (2000) 19, 4549 - 4552.