Epidermal growth factor induces expression of decay-accelerating factor in human colonic cancer cells via the mitogen-activated protein kinase pathway

Kazuaki Takeuchi, Motowo Mizuno, Tokurou Uesu, Junichirou Nasu, Mikihiro Kawada, Shinitirou Hori, Hiroyuki Okada, Yuichi Endo, Teizo Fujita, Takao Tsuji

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

The expression of decay-accelerating factor (DAF), a complement regulatory protein, is enhanced in colorectal cancer. In this study, to elucidate mechanisms for enhanced DAF expression, we studied the effects of growth factors on DAF expression in HT-29 human colonic cancer cells. Cells were treated with epidermal growth factor (EGF), insulin-like growth factor-I, platelet-derived growth factor, and transforming growth factor-β. DAF protein expression and mRNA expression were determined with enzyme immunoassay and Northern blot analysis. The signaling pathways that target DAF expression in response to growth factor stimulation were characterized by using various inhibitors of the signal transduction pathway. EGF induced significant increases in DAF protein and mRNA expression in HT-29 cells; the other growth factors had a weak effect or no effect. The EGF-induced DAF expression was inhibited by mitogen-activated protein (MAP) kinase kinase inhibitor PD 98059 but not by phosphatidylinositol-3 kinase inhibitor, phospholipase Cy inhibitor, or protein kinase C inhibitor. When we analyzed the phosphorylation state of the MAP kinase by immunoblot analysis, phosphorylated p44/p42 MAP kinase was detected in EGF-stimulated HT-29 cells, and the addition of PD 98059 abrogated the phosphorylation. These results indicate that EGF regulates DAF expression in HT-29 cells via the signaling pathway that depends on the activation of MAP kinase.

Original languageEnglish
Pages (from-to)186-192
Number of pages7
JournalJournal of Laboratory and Clinical Medicine
Volume138
Issue number3
DOIs
Publication statusPublished - Jan 1 2001

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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