Regulation of CFTR expression and function during differentiation of intestinal epithelial cells

CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco‐2 and HT‐29) show a lower level of CFTR mRNA, while a 10‐fold increase is seen in differentiated cells. These differences correlate well with those of o...

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Bibliographic Details
Published in:The EMBO journal 1992-07, Vol.11 (7), p.2487-2494
Main Authors: Sood, R., Bear, C., Auerbach, W., Reyes, E., Jensen, T., Kartner, N., Riordan, J.R., Buchwald, M.
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blotting, Western
Carrier Proteins - genetics
Cell Differentiation
cells
Colon - cytology
Colon - metabolism
cystic fibrosis
Cystic Fibrosis - metabolism
Cystic Fibrosis Transmembrane Conductance Regulator
differentiation
Epithelial Cells
Epithelium - metabolism
expression
function
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Expression Regulation
intestine
Iodine Radioisotopes - metabolism
Membrane Proteins - genetics
Microfilament Proteins - genetics
Molecular and cellular biology
Molecular genetics
regulation
RNA, Messenger - metabolism
Transcription, Genetic
transmembrane conductance regulator
Tumor Cells, Cultured
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Summary:CFTR, the protein defective in cystic fibrosis is regulated during differentiation of intestinal epithelial cells. The undifferentiated cells (Caco‐2 and HT‐29) show a lower level of CFTR mRNA, while a 10‐fold increase is seen in differentiated cells. These differences correlate well with those of other intestinal‐specific genes, including sucrase‐isomaltase, villin and alpha 1‐antitrypsin, indicating that the regulation is cell specific. In Caco‐2 cells the increase in CFTR mRNA cannot be accounted for by increased transcription of the gene. These data indicate that CFTR mRNA stabilizing factor(s) might be present in differentiated cells. The higher levels of CFTR mRNA in differentiated cells are accompanied by decreased protein levels, indicating, as well, involvement of translational control in the regulation of CFTR in these cells. Finally, fully differentiated cells show lowered levels of cyclic AMP‐activated C1‐ transport, the characteristic function of CFTR. Thus, CFTR function in differentiated cells is modulated by a complex interaction of regulatory elements. Caco‐2 and HT‐29 cells provide a suitable in vitro system in which to study the mechanism of regulation of CFTR.
ISSN:0261-4189
1460-2075
DOI:10.1002/j.1460-2075.1992.tb05313.x