Stimulation of Cdx1 by oncogenic β‐catenin/Tcf4 in colon cancer cells; opposite effect of the CDX2 homeoprotein

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Abstract
The homeobox gene Cdx1 is a regulator of intestinal epithelial cell proliferation and differentiation. Using a transfection approach, we showed here that the oncogenic activation of the β‐catenin pathway stimulates the endogenous expression of the Cdx1 mRNA as well as the activity of the Cdx1 promoter in cancer cells of the human colon. Reciprocally, the paralogue homeobox gene Cdx2 exerts an inhibitory effect on the basal and on the β‐catenin‐stimulated activity of the Cdx1 promoter. The inhibitory effect of CDX2 requires the intact homeodomain. It is not dependent on canonical CDX binding sites in the Cdx1 promoter nor on the cis‐elements specifically targeted by the β‐catenin/Tcf complex. We conclude that the oncogenically activated β‐catenin and CDX2 have opposite and independent effects on the Cdx1 homeobox gene.