in Human Colon Cancer by Insulin-like Growth Factor-I Regulation of Vascular Endothelial Growth Factor Expression

We investigated the role of insulin-like growth factor (IGF)-I and IGF-binding proteins (IGFBPs) in the regulation of vascular endothelial growth factor (VE(ìF)expression in colon cancer cells and the mechanism by which this regulation occurs. HT29 human colon cancer cells were treated with K.I -I for various time periods. VEGF mRNA expression increased within 2 h and peaked at 24 h. SYV620 colon cancer cells exhibited a peak induction of VEGF mRNA K h after IGF-I treatment. IGF-I induction of VEGF was confirmed at the protein level. In experi ments using transient transfection of VEGF promoter-reporter constructs into HT29 cells, IGF-I increased the activity of the VEGF promoter, and pretreatment of HT29 cells with dactinomycin abrogated the induction of VEGF mRNA 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 signif icantly modulate the effect of IGF-I induction of VEGF mRNA in HT29 cells. Treating cells with des-( 1-31-IGF-I (an active derivative of IGF-I that does not hind to binding proteins) had effects on VEGF mRNA expression that were similar to those of IGF-I. These findings suggest that IGF-I regulates Y'EGF expression in human colon cancer cells by induction of transcription of the VEGF gene. IGFBPs do not significantly affect IGF-I