Stimulation of Cdx1 by oncogenic beta-catenin/Tcf4 in colon cancer cells; opposite effect of the CDX2 homeoprotein.
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.
Domon-Dell
Claire
C
Institut National de la Santé et de la Recherche Médicale, Unité 381, 3 avenue Molière, 67200, Strasbourg, France.
Freund
Jean-Noël
JN
D000818:Animals; D000071616:CDX2 Transcription Factor; D018938:Caco-2 Cells; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology*; D019073:HT29 Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D011401:Promoter Regions, Genetic; D012334:RNA, Neoplasm / Q000096:biosynthesis; D051381:Rats; D020218:Response Elements; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000502:physiology; D015533:Transcriptional Activation; D014162:Transfection; D051176:beta Catenin
C491273:CDX1 protein, human; D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; C495270:CTNNB1 protein, human; C491271:Cdx1 protein, rat; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D015513:Oncogene Proteins; D012334:RNA, Neoplasm; D051820:TCF Transcription Factors; C544894:TCF7L2 protein, human; C553059:Tcf7l2 protein, rat; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051176:beta Catenin