Homeodomain protein CDX2 regulates COX-2 expression in colorectal cancer.

CDX2 is an intestine-specific tumor suppressor gene encoding homeodomain-containing transcription factor, which is involved in a variety of developmental, proliferating, and differentiating processes. Moreover, the expression of CDX2 is reduced in a subset of primary colorectal cancers. In contrast, cyclooxygenase-2 (COX-2) is often up-regulated in human colorectal cancers. However, the ...
molecular relationship between CDX2 down-regulation and COX-2 up-regulation is unknown. Here we show that CDX2 down-regulates COX-2 promoter activity by interacting with NF-kappaB. The ectopic expression of CDX2 was found to suppress PMA-induced COX-2 promoter activity in a dose-dependent manner. In addition, the treatment of colorectal cancer cells with PMA resulted in significant reduction in the level of endogenous CDX2 and a significant increase in the level of endogenous COX-2, in a dose-dependent manner. Furthermore, CDX2 was found to co-immunoprecipitate with the p65 subunit of NF-kappaB and to inhibit p65-induced NF-kappaB minimal promoter activity in colon cancer cells. These results suggest that reduced CDX2 expression may be involved in colorectal carcinogenesis by enhancing NF-kappaB-mediated inflammatory genes such as COX-2.
Mesh Terms:
Caco-2 Cells, Cell Line, Colorectal Neoplasms, Cyclooxygenase 2, Dose-Response Relationship, Drug, Gene Expression Regulation, Genes, Reporter, Homeodomain Proteins, Humans, Immunoglobulin kappa-Chains, Interferon Type I, Isoenzymes, Luciferases, Membrane Proteins, NF-kappa B, Plasmids, Promoter Regions, Genetic, Prostaglandin-Endoperoxide Synthases, Tetradecanoylphorbol Acetate, Trans-Activators, Transfection, eIF-2 Kinase
Biochem. Biophys. Res. Commun.
Date: Feb. 27, 2004
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