REGULATION OF VASCULAR ENDOTHELIAL GROWTH-FACTOR EXPRESSION IN HUMAN COLON-CANCER BY INSULIN-LIKE GROWTH-FACTOR-I

We investigated the role of insulin-like growth factor (IGF)-I and IGF -binding proteins (IGFBPs) in the regulation of vascular endothelial g rowth factor (VEGF) expression in colon cancer cells and the mechanism by which this regulation occurs. HT29 human colon cancer cells were t reated with IGF-I for various time periods. VEGF mRNA expression incre ased within 2 h and peaked at 24 h. SW620 colon cancer cells exhibited a peak induction of VEGF mRNA 8 h after IGF-I treatment. IGF-I induct ion of VEGF was confirmed at the protein level. In experiments using t ransient transfection of VEGF promoter-reporter constructs into HT29 c ells, IGF-I increased the activity of the VEGF promoter, and pretreatm ent of HT29 cells with dactinomycin abrogated the induction of VEGF mR NA by IGF-I. The half-life of VEGF mRNA was not prolonged by treatment with IGF-I. Blocking the activity of IGFBP-4 did not significantly mo dulate the effect of IGF-I induction of VEGF mRNA in HT29 cells. Treat ing cells with des-(1-3)-IGF-I (an active derivative of IGF-I that doe s not bind to binding proteins) had effects on VEGF mRNA expression th at were similar to those of IGF-I. These findings suggest that IGF-I r egulates VEGF expression in human colon cancer cells by induction of t ranscription of the VEGF gene. IGFBPs do not significantly affect IGF- I induction of VEGF.