The transcription factor Net regulates the angiogenic switch.
Fiche publication
Date publication
septembre 2003
Auteurs
Membres identifiés du Cancéropôle Est :
Dr WASYLYK Bohdan
Tous les auteurs :
Zheng H, Wasylyk C, Ayadi A, Abecassis J, Schalken JA, Rogatsch H, Wernert N, Maira SM, Multon MC, Wasylyk B
Lien Pubmed
Résumé
Angiogenesis is fundamental to physiological and pathological processes. Despite intensive efforts, little is known about the intracellular circuits that regulate angiogenesis. The transcription factor Net is activated by phosphorylation induced by Ras, an indirect regulator of angiogenesis. Net is expressed at sites of vasculogenesis and angiogenesis during early mouse development, suggesting that it could have a role in blood vessel formation. We show here that down-regulation of Net inhibits angiogenesis and vascular endothelial growth factor (VEGF) expression in vivo, ex vivo, and in vitro. Ras-activated phosphorylated Net (P-Net) stimulates the mouse VEGF promoter through the -80 to -53 region that principally binds Sp1. P-Net and VEGF are coexpressed in angiogenic processes in wild-type mouse tissues and in human tumors. We conclude that Net is a regulator of angiogenesis that can switch to an activator following induction by pro-angiogenic molecules.
Référence
Genes Dev. 2003 Sep 15;17(18):2283-97.