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Scientific article
English

Differential expression of cell-cell adhesion proteins and cyclin D in MEK1-transdifferentiated MDCK cells

Published inAmerican journal of physiology. Cell physiology, vol. 279, no. 5, p. C1472-1482
Publication date2000
Abstract

Overexpression of a constitutively active mutant of the mitogen-activated protein kinase kinase MEK1 (caMEK1) in epithelial Madin-Darby canine kidney (MDCK)-C7 cells disrupts morphogenesis, induces an invasive phenotype, and is associated with a reduced rate of cell proliferation. The role of cell-cell adhesion molecules and cell cycle proteins in these processes, however, has not been investigated. We now report loss of E-cadherin expression as well as a marked reduction of beta- and alpha-catenin expression in transdifferentiated MDCK-C7 cells stably expressing caMEK1 (C7caMEK1) compared with epithelial mock-transfected MDCK-C7 (C7Mock1) cells. At least part of the remaining alpha-catenin was coimmunoprecipitated with beta-catenin, whereas no E-cadherin was detected in beta-catenin immunoprecipitates. In both cell types, the proteasome-specific protease inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) and lactacystin led to a time-dependent accumulation of beta-catenin, including the appearance of high-molecular-weight beta-catenin species. Quiescent as well as serum-stimulated C7caMEK1 cells showed a higher cyclin D expression than epithelial C7Mock1 cells. The MEK inhibitor U-0126 inhibited extracellular signal-regulated kinase phosphorylation and cyclin D expression in C7caMEK1 cells and almost abolished their already reduced cell proliferation rate. We conclude that the transdifferentiated and invasive phenotype of C7caMEK1 cells is associated with a diminished expression of proteins involved in cell-cell adhesion. Although beta-catenin expression is reduced, C7caMEK1 cells show a higher expression of U-0126-sensitive cyclin D protein.

Keywords
  • Animals
  • Cadherins/metabolism
  • Cell Adhesion Molecules/metabolism
  • Cell Differentiation/physiology
  • Cell Division/physiology
  • Cell Line/cytology
  • Cyclins/metabolism
  • Cysteine Endopeptidases/physiology
  • Cytoskeletal Proteins/metabolism
  • Dogs
  • Kidney/cytology/metabolism
  • MAP Kinase Kinase 1
  • Mitogen-Activated Protein Kinase Kinases/genetics/physiology
  • Multienzyme Complexes/physiology
  • Peptide Hydrolases/metabolism
  • Proteasome Endopeptidase Complex
  • Protein-Serine-Threonine Kinases/genetics/physiology
  • Trans-Activators
  • Transfection
  • Alpha Catenin
  • Beta Catenin
Citation (ISO format)
MARSCHITZ, Ingrid et al. Differential expression of cell-cell adhesion proteins and cyclin D in MEK1-transdifferentiated MDCK cells. In: American journal of physiology. Cell physiology, 2000, vol. 279, n° 5, p. C1472–1482.
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ISSN of the journal0363-6143
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