Inhibition of sucrose-isomaltase expression by EGF in the human colon adenocarcinoma cells Caco-2.
To investigate the role and mechanism of action of epidermal growth factor (EGF) in the intestinal epithelium, we have studied its influence on proliferation and differentiation of Caco-2 cells, a human colon adenocarcinoma cell line exhibiting several characteristics of adult small intestinal enterocytes. A clone of Caco-2 cells synthesizing minimal amounts of transforming growth factor-alpha (TGF-alpha)/epidermal growth factor (EGF)-like activity was used in these studies. Cells grown in the presence of 20-200 ng EGF/ml exhibited increased DNA synthesis and proliferation; formation of morphologically poorly differentiated multilayers was observed at 200 ng EGF/ml. At all concentrations tested EGF produced a significant and marked reduction in sucrase activity, whereas other brush-border enzymes (aminopeptidase N, alkaline phosphatase, dipeptidylpeptidase IV) were only marginally affected. EGF influenced sucrase expression at two different levels. At 20 ng/ml, it affected primarily sucrase-isomaltase processing in the endoplasmic reticulum and/or increased its degradation. At 200 ng EGF/ml, a significant and marked reduction in sucrase-isomaltase mRNA levels and biosynthesis was observed. These results demonstrated that EGF has important and selective effects on Caco-2 cell proliferation and differentiation and may affect different cellular activities depending on its concentration.
Cross
H S
HS
Section of Physiology, Cornell University, Ithaca, New York 14853.
Quaroni
A
A
D000230:Adenocarcinoma; D000911:Antibodies, Monoclonal; D002454:Cell Differentiation; D002455:Cell Division; D003110:Colonic Neoplasms; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D008854:Microscopy, Electron; D008871:Microvilli / Q000201:enzymology; D011233:Precipitin Tests; D013394:Sucrase-Isomaltase Complex / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D004815:Epidermal Growth Factor; D013394:Sucrase-Isomaltase Complex