Regulation of vascular endothelial growth factor expression in human colon cancer by interleukin-1beta.

Abstract

Expression of vascular endothelial growth factor (VEGF), an important angiogenic factor in colon cancer, is tightly regulated by factors in the microenvironment. However, specific factors indigenous to the organ microenvironment of colon cancer growth that regulate VEGF expression in human colon cancer are not well defined. We investigated interleukin-1β (IL-1β) induction of VEGF expression in colon cancer cells and the mechanism by which this occurs. HT29 human colon cancer cells were treated with IL-1β for various periods. Induction of VEGF mRNA by IL-1β peaked at 24 h (> fivefold) and returned to baseline by 48 h. SW620 human colon cancer cells also reached a peak induction of VEGF mRNA 24 h after treatment with IL-1β. VEGF was induced at a dose range between 1 and 20 ng ml−1 of IL-1β. IL-1β induction of VEGF was also confirmed at the protein level. To examine the mechanism for VEGF induction by IL-1β, we transiently transfected VEGF promoter-reporter constructs into HT29 cells. IL-1β increased the activity of the VEGF promoter-reporter construct. Pretreatment of HT29 cells with dactinomycin abrogated the induction of VEGF mRNA by IL-1β. The half-life of VEGF mRNA was not prolonged by treatment with IL-1β. These findings suggest that IL-1β regulates VEGF expression in human colon cancer cells by increasing transcription of the VEGF gene. © 1999 Cancer Research Campaign