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Growth inhibition and differentiation of the human colon carcinoma cell line, Caco‐2, by constitutive expression of insulin‐like growth factor binding protein‐3
Author(s) -
Macdonald Richard,
Schaffer Beverly,
Kang IlJun,
Hong Soon,
Kim Eun,
Park Jung
Publication year - 1999
Publication title -
journal of gastroenterology and hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.214
H-Index - 130
eISSN - 1440-1746
pISSN - 0815-9319
DOI - 10.1046/j.1440-1746.1999.01803.x
Subject(s) - transfection , insulin like growth factor binding protein , cell culture , growth factor , enterocyte , caco 2 , biology , microbiology and biotechnology , cellular differentiation , cell growth , endocrinology , insulin like growth factor , medicine , gene , biochemistry , receptor , small intestine , genetics
The human colon carcinoma cell line, Caco‐2, produces insulin‐like growth factor binding protein‐3 (IGFBP‐3), the secretion of which correlates with markers of enterocyte differentiation. To investigate whether IGFBP‐3 inhibits proliferation or induces differentiation, Caco‐2 cells were stably transfected with an IGFBP‐3 cDNA expression construct or pcDNA3 vector as a control. Accumulation of IGFBP‐3 mRNA and secretion of the protein into conditioned medium 9 days after plating were readily detected in the transfected cells, whereas these parameters were undetectable in pcDNA3‐transfected cells. Insulin‐like growth factor binding protein‐3‐expressing cells grew at a rate similar to the controls for 6 days after plating, but achieved a much lower final density between days 10 and 12. By day 9 of culture, accumulation of sucrase‐isomaltase mRNA, a marker of enterocytic differentiation of Caco‐2 cells, was evident in the IGFBP‐3‐expressing cells, but was undetectable in the controls. These results indicate that IGFBP‐3 may inhibit proliferation and induce early differentiation of Caco‐2 cells.