Inhibition of NF-kappaB activation and chemokine expression by the leukocyte glycoprotein, CD43, in colon cancer cells

CD43 is a heavily O-glycosylated type I trans-membrane 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 tetracycli...

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Veröffentlicht in:	International journal of oncology 2006-03, Vol.28 (3), p.695-704
Hauptverfasser:	Laos, Sirle, Baeckström, Dan, Hansson, Gunnar C
Format:	Artikel
Sprache:	eng
Schlagworte:	Active Transport Active Transport, Cell Nucleus - drug effects antagonists & inhibitors Antigens Blotting Blotting, Western CD43 Cell Line Cell Line, Tumor Cell Nucleus Cell Nucleus - drug effects Cell Nucleus - metabolism Chemokine CCL2 Chemokine CCL2 - genetics Chemokine CCL2 - metabolism Chemokine CXCL1 Chemokines Chemokines - genetics Chemokines - metabolism Chemokines, CXC - genetics Chemokines, CXC - metabolism Colonic Neoplasms Colonic Neoplasms - genetics Colonic Neoplasms - metabolism Colonic Neoplasms - pathology CXC drug effects Enzyme-Linked Immunosorbent Assay Flow Cytometry Gene Expression Regulation Gene Expression Regulation, Neoplastic - genetics genetics Humans I-kappa B Proteins I-kappa B Proteins - metabolism Intercellular Signaling Peptides and Proteins Intercellular Signaling Peptides and Proteins - genetics Intercellular Signaling Peptides and Proteins - metabolism Interleukin-8 Interleukin-8 - genetics Interleukin-8 - metabolism Leukosialin - genetics Leukosialin - metabolism MEDICAL AND HEALTH SCIENCES MEDICIN OCH HÄLSOVETENSKAP Messenger metabolism Neoplastic NF-kappa B NF-kappa B - antagonists & inhibitors NF-kappa B - genetics NF-kappa B - metabolism NF-KappaB Inhibitor alpha pathology pharmacology PPAR gamma PPAR gamma - metabolism RNA RNA, Messenger - genetics RNA, Messenger - metabolism Time Factors Transcription Factor RelA Transcription Factor RelA - genetics Transcription Factor RelA - metabolism Tumor Tumor Necrosis Factor-alpha Tumor Necrosis Factor-alpha - pharmacology Western
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Zusammenfassung:	CD43 is a heavily O-glycosylated type I trans-membrane 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-kappaB activation and reduced the DNA binding of transcription factor p65 but not p50. Furthermore, a reduced NF-kappaB responsive promoter activity was observed and a decreased expression of proinflammatory chemokines MCP-1, IL-8 and GRO-alpha. These results suggest that overexpression of CD43 suppresses a subset of NF-kappaB target genes, partly via the inhibition of p65 transcriptional activity.
ISSN:	1019-6439