PGE(2) stimulates VEGF expression in endothelial cells via ERK2/JNK1 signaling pathways

Vascular endothelial growth factor (VEGF) plays an essential role in the in itiation and regulation of angiogenesis-a crucial component of wound healin g and cancer growth. Prostaglandins (PGs) stimulate angiogenesis but the pr ecise mechanisms of their pro-angiogenic actions remain unexplained. We inv estigated whether prostaglandin E-2 (PGE(2)) can induce VEGF expression in rat gastric microvascular endothelial cells (RGMEC) and the signaling pathw ay(s) involved. We demonstrated that PGE, significantly increased ERK2 and JNK1 activation and VEGF mRNA and protein expression. Incubation of RGMEC w ith PD 98059 (MEK kinase inhibitor) significantly reduced PGE(2)-induced ER K2 activity, VEGF mRNA and protein expression. Furthermore, PD 98059 treatm ent almost completely abolished JNK1 activation. Our data suggest that PGE( 2)-stimulates VEGF expression in RGMEC via transactivation of JNK1 by ERK2. One potential implication of this finding is that increased PG levels in c ancers could facilitate tumor growth by stimulating VEGF synthesis and angi ogenesis. (C) 2001 Academic Press.