Stimulation of Cdx1 by oncogenic beta-catenin/Tcf4 in colon cancer cells; opposite effect of the CDX2 homeoprotein.

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 beta-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 beta-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 beta-catenin/Tcf complex. We conclude that the oncogenically activated beta-catenin and CDX2 have opposite and independent effects on the Cdx1 homeobox gene.
Authors	Claire Domon-Dell, Jean-Noël Freund
Journal	FEBS letters (FEBS Lett) Vol. 518 Issue 1-3 Pg. 83-7 (May 08 2002) ISSN: 0014-5793 [Print] England
PMID	11997022 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	CDX1 protein, human CDX2 Transcription Factor CDX2 protein, human CTNNB1 protein, human Cdx1 protein, rat Ctnnb1 protein, rat Cytoskeletal Proteins Homeodomain Proteins Oncogene Proteins RNA, Neoplasm TCF Transcription Factors TCF7L2 protein, human Tcf7l2 protein, rat Trans-Activators Transcription Factor 7-Like 2 Protein Transcription Factors beta Catenin
Topics	Animals CDX2 Transcription Factor Caco-2 Cells Cell Line Colonic Neoplasms (genetics, metabolism) Cytoskeletal Proteins (antagonists & inhibitors, physiology) HT29 Cells Homeodomain Proteins (biosynthesis, genetics, physiology) Humans Oncogene Proteins (antagonists & inhibitors, physiology) Promoter Regions, Genetic RNA, Neoplasm (biosynthesis) Rats Response Elements TCF Transcription Factors Trans-Activators Transcription Factor 7-Like 2 Protein Transcription Factors (physiology) Transcriptional Activation Transfection beta Catenin

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