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 protein 3 (IGFBP-3) in normal human colonic epithelium and whether IGFBP-3 is involved 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 increased differentiation and apoptosis. Treatment of human colonic tumor cell lines with IGFBP-3 alone was shown to have no effect on growth. However, an increase in p53-dependent apoptosis was observed in the presence of 100 ng/ml IGFBP-3 24 h after the induction of DNA damage by gamma-irradiation. These results suggest that IGFBP-3 enhances the p53-dependent apoptotic response of colorectal cells to DNA damage.
Williams
A C
AC
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, United Kingdom. A.C.Williams@bristol.ac.uk
Collard
T J
TJ
Perks
C M
CM
Newcomb
P
P
Moorghen
M
M
Holly
J M
JM
Paraskeva
C
C
D000230:Adenocarcinoma / Q000378:metabolism / Q000503:physiopathology; D000236:Adenoma / Q000378:metabolism / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism / Q000503:physiopathology*; D004249:DNA Damage; D016158:Genes, p53 / Q000502:physiology*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000494:pharmacology / Q000502:physiology*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D009363:Neoplasm Proteins / Q000494:pharmacology / Q000502:physiology*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018972:Insulin-Like Growth Factor Binding Protein 3; D009363:Neoplasm Proteins