title: Ultraviolet irradiation can induce evasion of colon cancer cells from stimulation of epidermal growth factor.
abstract: Receptor down-regulation is the most prominent regulatory system of EGF receptor (EGFR) signal attenuation and a critical target for therapy against colon cancer, which is highly dependent on the function of the EGFR. In this study, we investigated the effect of ultraviolet-C (UV-C) on down-regulation of EGFR in human colon cancer cells (SW480, HT29, and DLD-1). UV-C caused inhibition of cell survival and proliferation, concurrently inducing the decrease in cell surface EGFR and subsequently its degradation. UV-C, as well as EGFR kinase inhibitors, decreased the expression level of cyclin D1 and the phosphorylated level of retinoblastoma, indicating that EGFR down-regulation is correlated to cell cycle arrest. Although UV-C caused a marked phosphorylation of EGFR at Ser-1046/1047, UV-C also induced activation of p38 MAPK, a stress-inducible kinase believed to negatively regulate tumorigenesis, and the inhibition of p38 MAPK canceled EGFR phosphorylation at Ser-1046/1047, as well as subsequent internalization and degradation, suggesting that p38 MAPK mediates EGFR down-regulation by UV-C. In addition, phosphorylation of p38 MAPK induced by UV-C was mediated through transforming growth factor-β-activated kinase-1. Moreover, pretreatment of the cells with UV-C suppressed EGF-induced phosphorylation of EGFR at tyrosine residues in addition to cell survival signal, Akt. Together, these results suggest that UV-C irradiation induces the removal of EGFRs from the cell surface that can protect colon cancer cells from oncogenic stimulation of EGF, resulting in cell cycle arrest. Hence, UV-C might be applied for clinical strategy against human colon cancers.
authors.affiliation: Department of Pharmacology, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. seijiadachi0123@gmail.com
authors.forename: Seiji
authors.initials: S
authors.lastname: Adachi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yasuda
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakashima
authors.forename: Takahiro
authors.initials: T
authors.lastname: Yamauchi
authors.forename: Junji
authors.initials: J
authors.lastname: Kawaguchi
authors.forename: Masahito
authors.initials: M
authors.lastname: Shimizu
authors.forename: Masahiko
authors.initials: M
authors.lastname: Itani
authors.forename: Momoko
authors.initials: M
authors.lastname: Nakamura
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nishii
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Hirose
authors.forename: Yukio
authors.initials: Y
authors.lastname: Okano
authors.forename: Hisataka
authors.initials: H
authors.lastname: Moriwaki
authors.forename: Osamu
authors.initials: O
authors.lastname: Kozawa
mesh_terms: D001483:Base Sequence; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019938:Cyclin D1 / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects / Q000528:radiation effects; D012694:Serine / Q000378:metabolism; D014466:Ultraviolet Rays; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D019938:Cyclin D1; D012694:Serine; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D048051:p38 Mitogen-Activated Protein Kinases