Inhibition of NF-κB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells
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- Published online on: March 1, 2006 https://doi.org/10.3892/ijo.28.3.695
- Pages: 695-704
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Abstract
CD43 is a heavily O-glycosylated type I transmembrane protein, expressed at high levels on the surface of leukocytes. It is frequently overexpressed in early colon adenomas, but not in normal colon epithelial cells. To identify CD43 target genes, gene array analysis was performed using a tetracycline-inducible CD43 expression system in human colon adenocarcinoma SW480 cells. CD43 was demonstrated to down-regulate a variety of chemokine genes. Overexpression of CD43 suppressed constitutive as well as PMA-induced NF-κB activation and reduced the DNA binding of transcription factor p65 but not p50. Furthermore, a reduced NF-κB responsive promoter activity was observed and a decreased expression of proinflammatory chemokines MCP-1, IL-8 and GRO-α. These results suggest that overexpression of CD43 suppresses a subset of NF-κB target genes, partly via the inhibition of p65 transcriptional activity.
