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Institut National de la Santé et de la Recherche Médicale, Unité 381, 67200 Strasbourg, France
To explore the role of homeobox genes in
the intestine, the human colon adenocarcinoma cell line
Caco2-TC7 has been stably transfected with plasmids
synthesizing Cdx1 and Cdx2 sense and antisense RNAs.
Cdx1 overexpression or inhibition by antisense RNA
does not markedly modify the cell differentiation markers analyzed in this study. In contrast, Cdx2 overexpression stimulates two typical markers of enterocytic differentiation: sucrase-isomaltase and lactase. Cells in
which the endogenous expression of Cdx2 is reduced by
antisense RNA attach poorly to the substratum. Conversely, Cdx2 overexpression modifies the expression
of molecules involved in cell-cell and cell-substratum
interactions and in transduction process: indeed, E-cadherin, integrin- Laminin-1 is known to stimulate intestinal cell differentiation in vitro. In the present study, we demonstrate
that the differentiating effect of laminin-1 coatings on
Caco2-TC7 cells is accompanied by an upregulation of
Cdx2. To further document this observation, we analyzed a series of Caco2 clones in which the production
of laminin- Taken together, these results suggest (a) that Cdx1
and Cdx2 homeobox genes play distinct roles in the intestinal epithelium, (b) that Cdx2 provokes pleiotropic
effects triggering cells towards the phenotype of differentiated villus enterocytes, and (c) that Cdx2 expression is modulated by basement membrane components. Hence, we conclude that Cdx2 plays a key role in the
extracellular matrix-mediated intestinal cell differentiation.
4 subunit, laminin-
2 chain, hemidesmosomal protein, APC, and 
-actinin are upregulated.
Interestingly, most of these molecules are preferentially
expressed in vivo in the differentiated villi enterocytes
rather than in crypt cells. Cdx2 overexpression also results in the stimulation of HoxA-9 mRNA expression,
an homeobox gene selectively expressed in the colon.
In contrast, Cdx2-overexpressing cells display a decline of Cdx1 mRNA, which is mostly found in vivo in crypt
cells. When implanted in nude mice, Cdx2-overexpressing cells produce larger tumors than control cells, and
form glandular and villus-like structures.
1 chain is differentially inhibited by antisense RNA. We found a positive correlation between
the level of Cdx2 expression, that of endogenous laminin-1 chain mRNA and that of sucrase-isomaltase expression in these cell lines.
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