Regulation of vascular endothelial growth factor expression by acidosis inhuman cancer cells

The influence of acidosis on the expression of the vascular endothelial gro wth factor (VEGF) gene was determined, FG human pancreatic adenocarcinoma c ells were incubated for various time periods in media at a physiologically relevant pH level (6.7-7.4), The expression of VEGF mRNA and protein secret ion was inversely correlated with pH in a pH- and time-dependent manner. Tr ansient acidosis also activated the VEGF promoter/enhancer luciferase repor ter, which was consistent with an increased VEGF gene transcription rate an d VEGF mRNA half-life. These data indicated that acidosis transcriptionally and posttranscriptionally regulates VEGF expression, suggesting that an ac idic tumor microenvironment contributes to tumor angiogenesis and progressi on.