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

Abstract：

: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.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Kim SP,Park JW,Lee SH,Lim JH,Jang BC,Lee SH,Jang IH,Freund JN,Suh SI,Mun KC,Song DK,Ha EM,Lee WJ,Kwon TK

doi

10.1016/j.bbrc.2004.01.020

subject

Has Abstract

pub_date

2004-02-27 00:00:00

pages

93-9

issue

1

eissn

0006-291X

issn

1090-2104

pii

S0006291X04000464

journal_volume

315

pub_type

杂志文章

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