title: Inhibition of E-cadherin dependent cell-cell contact promotes MUC5AC mucin production through the activation of epidermal growth factor receptors.
abstract: Mucin production by epithelial cells is modulated by many soluble factors, including epidermal growth factor (EGF). E-Cadherin promotes EGF receptor (EGFR)-mediated MUC5AC mucin production in airway epithelial cells in dense cultures, suggesting the involvement of E-cadherin in activating EGFRs and mucin production. However, the role of E-cadherin in modulating mucin production is not completely understood. We examined its role in MUC5AC production in a human lung epithelial cell line, NCI-H292. Treatment of low density NCI-H292 cells with an anti-E-cadherin monoclonal antibody (SHE78-7) inhibited cell-cell contact in the dispersed colonies, but promoted MUC5AC production. Furthermore, treatment of the NCI-H292 cells with anti-E-cadherin antibody stimulated phosphorylation of extracellular signal-regulated kinase (ERK). The enhanced production of MUC5AC was inhibited with an EGFR inhibitor and with a MEK inhibitor, but not with a Src family kinase inhibitor. These results suggest that inhibition of E-cadherin activates EGFRs independently of Src and promotes MUC5AC production through the ERK signaling pathway in sparsely cultured NCI-H292 cells.
authors.affiliation: Molecular Biology Laboratory, Faculty of Bioresource Sciences, Akita Prefectural University, Japan. jun_iwashita@akita-pu.ac.jp
authors.forename: Jun
authors.initials: J
authors.lastname: Iwashita
authors.forename: Kyohei
authors.initials: K
authors.lastname: Ose
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ito
authors.forename: Jun
authors.initials: J
authors.lastname: Murata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Abe
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015820:Cadherins / Q000276:immunology / Q000378:metabolism*; D002450:Cell Communication / Q000276:immunology; D002452:Cell Count; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D055271:Mucin 5AC / Q000096:biosynthesis*; D010766:Phosphorylation; D015398:Signal Transduction
chemical_list: D000911:Antibodies, Monoclonal; D015820:Cadherins; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases