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

Marschitz, Ingrid
Lechner, Judith
Mosser, Irene
Dander, Martina
Schramek, Herbert
Published in American Journal of Physiology. Cell Physiology. 2000, vol. 279, no. 5, p. C1472-82
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 AnimalsCadherins/metabolismCell Adhesion Molecules/metabolismCell Differentiation/physiologyCell Division/physiologyCell Line/cytologyCyclins/metabolismCysteine Endopeptidases/physiologyCytoskeletal Proteins/metabolismDogsKidney/cytology/metabolismMAP Kinase Kinase 1Mitogen-Activated Protein Kinase Kinases/genetics/physiologyMultienzyme Complexes/physiologyPeptide Hydrolases/metabolismProteasome Endopeptidase ComplexProtein-Serine-Threonine Kinases/genetics/physiologyTrans-ActivatorsTransfectionAlpha CateninBeta Catenin
PMID: 11029295
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Other version: http://ajpcell.physiology.org/cgi/content/full/279/5/C1472
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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. C1472-82. https://archive-ouverte.unige.ch/unige:3916

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Deposited on : 2009-10-26

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