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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CDX2 Transcription Factor
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Caco-2 Cells
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Cell Line
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Colonic Neoplasms / genetics
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Colonic Neoplasms / metabolism*
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Cytoskeletal Proteins / antagonists & inhibitors*
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Cytoskeletal Proteins / physiology*
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HT29 Cells
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Homeodomain Proteins / biosynthesis
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Homeodomain Proteins / genetics*
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Homeodomain Proteins / physiology*
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Humans
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Oncogene Proteins / antagonists & inhibitors
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Oncogene Proteins / physiology
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Promoter Regions, Genetic
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RNA, Neoplasm / biosynthesis
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Rats
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Response Elements
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TCF Transcription Factors
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Trans-Activators*
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Transcription Factor 7-Like 2 Protein
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Transcription Factors / physiology
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Transcriptional Activation
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Transfection
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beta Catenin
Substances
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CDX1 protein, human
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CDX2 Transcription Factor
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CDX2 protein, human
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CTNNB1 protein, human
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Cdx1 protein, rat
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Ctnnb1 protein, rat
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Cytoskeletal Proteins
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Homeodomain Proteins
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Oncogene Proteins
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RNA, Neoplasm
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TCF Transcription Factors
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TCF7L2 protein, human
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Tcf7l2 protein, rat
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Trans-Activators
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Transcription Factor 7-Like 2 Protein
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Transcription Factors
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beta Catenin