Platelet-derived growth factor and phorbol ester cause an increase in vascular endothelial growth factor (VEGF) mRNA expression in control NIH 3T3 fibroblasts and NIH 3T3 fibroblasts overexpressing human protein kinase C (PKC) alpha. In the case of phorbol ester-induced VEGF expression, the VEGF mRNA levels were significantly higher in cells overexpressing human PKC alpha as compared to control cells. In cells stimulated with platelet-derived growth factor or phorbol ester, induction of expression was lost after down-regulation of PKC. This indicates that PKC is involved in the signal transduction leading to VEGF expression.