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Marschitz, I; Lechner, J; Mosser, I; Dander, M; Montesano, R; Schramek, H.
Differential expression of cell-cell adhesion proteins and cyclin D in MEK1-transdifferentiated MDCK cells.
Am J Physiol Cell Physiol. 2000; 279(5):C1472-C1482 Doi: 10.1152/ajpcell.2000.279.5.C1472 [OPEN ACCESS]
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Leading authors Med Uni Graz
Marschitz Ingrid Christine
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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.
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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 - metabolism
Kidney - cytology
MAP Kinase Kinase 1 - cytology
Mitogen-Activated Protein Kinase Kinases - genetics
Multienzyme Complexes - physiology
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Proteasome Endopeptidase Complex - metabolism
Protein-Serine-Threonine Kinases - genetics
Research Support, Non-U.S. Gov't - genetics
Trans-Activators - genetics
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alpha Catenin - genetics
beta Catenin - genetics

Find related publications in this database (Keywords)
extracellular signal-regulated kinase
differentiation
proliferation
E-cadherin
beta-catenin
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