Cell cycle protein suppression and p21 induction in differentiating
caco2 cells.
Evers, B. Mark, Tien C. Ko, Jing Li, E. Aubrey Thompson.
Department of Surgery and Department of Human Biological Chemistry
and Genetics, The University of Texas Medical Branch, Galveston,
Texas 77555
APStracts 3:0145G, 1996.
Despite intensive efforts, the exact cellular mechanisms leading to
gut differentiation and development remain largely undefined. The
cyclins, the cyclin-dependent kinases (Cdks), and the Cdk inhibitors
(e.g. p21 and p27) are proteins that are important for cell cycle
progression, subsequent growth inhibition and differentiation of
various cell types. The purpose of our study was to better define the
role of these cell cycle proteins in gut differentiation using the
CaCo2 human cell line which spontaneously differentiates to a small
bowel phenotype, as demonstrated by induction of sucrase-isomaltase
(SI) gene expression. We found that protein levels of the cyclins
(both D-type and E) and the Cdks (both Cdk2 and 4) progressively
decreased in postconfluent CaCo2 cells. Moreover, cyclin E-associated
histone H1 kinase activity decreased in an analogous fashion as the
cyclins and Cdks. In contrast, induction of the Cdk inhibitor p21
occurred by 3 days postconfluency which was prior to increases of SI
mRNA levels. These changes in the cell cycle proteins which include a
progressive decrease of the cyclins and Cdks and a concomitant
induction of p21 suggest an important role for these proteins in
CaCo2 cell differentiation. Identifying the cell cycle mechanisms
responsible for intestinal cell differentiation will be important to
our understanding of both normal gut development as well as gut
neoplasia which involves aberrant regulation of cell cycle arrest.
Received 26 February 1996; accepted in final form 12 July 1996.
APS Manuscript Number G74-6.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 4 August 1996