Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells

We investigated the expression of insulin-like growth factor binding protei n 3 (IGFBP-3) in normal human colonic epithelium and whether IGFBP-3 is inv olved in the induction of apoptosis in colonic epithelial cells. A gradient of IGFBP-3 protein expression was observed within the normal colonic crypt , and increased IGFBP-3 expression was coincident with the region of increa sed differentiation and apoptosis, Treatment of human colonic tumor cell li nes with IGFBP-3 alone was shown to have no effect on growth, However, an i ncrease in p53-dependent apoptosis was observed in the presence of 100 ng/m l IGFBP-3 24 h after the induction of DNA damage by gamma-irradiation, Thes e results suggest that IGFBP-3 enhances the p53-dependent apoptotic respons e of colorectal cells to DNA damage.