Protein kinase C signalling pathway is involved in the regulation of vascular endothelial growth factor expression in human bladder transitional carcinoma cells

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor ass ociated with the growth and metastasis of various cancers and plays a promi nent role in vesical angiogenesis regulation. In this study, we investigate d the effect of the phorbol 12-myristate 13-acetate (PMA) on the expression of VEGF in human bladder transitional carcinoma cells (RT4). RT4 cells exp ressed three VEGF isoforms (VEGF(189), VEGF(165), VEGF(121)). PMA increased VEGF mRNA expression time-dependently with a peak at 4 h. PMA increased th e half-life of VEGF mRNA. The amount of VEGF protein in conditioned media w as increased by PMA in a dose-dependent manner with a maximal effect at 10( -7) M. Staurosporine and calphostin C (PKC inhibitors) decreased PMA-induce d VEGF mRNA expression as opposed to protein kinase A or cyclic nucleotide- dependent protein kinase inhibitors. Thus, in RT4 cells, VEGF expression is up-regulated by PMA via the PKC signalling pathway and according to a post transcriptional mechanism. (C) 2001 Elsevier Science Inc. All rights reserv ed.