Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / metabolism
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Adenocarcinoma / physiopathology
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Adenoma / metabolism
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Adenoma / physiopathology
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Apoptosis / drug effects
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Apoptosis / genetics
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Apoptosis / physiology*
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Cell Survival / genetics
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Cell Survival / physiology
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Colon / drug effects
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Colon / metabolism
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Colonic Neoplasms / metabolism
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Colonic Neoplasms / physiopathology*
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DNA Damage
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Genes, p53 / physiology*
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Humans
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Insulin-Like Growth Factor Binding Protein 3 / pharmacology
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Insulin-Like Growth Factor Binding Protein 3 / physiology*
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Intestinal Mucosa / drug effects
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Intestinal Mucosa / metabolism
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Neoplasm Proteins / pharmacology
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Neoplasm Proteins / physiology*
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Tumor Cells, Cultured / drug effects
Substances
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Insulin-Like Growth Factor Binding Protein 3
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Neoplasm Proteins