Suppression of cell growth by ectopic expression of N-cadherin |
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Authors: | X Wang AA Thant K Machida Y Hiraiwa H Iwata S Matsuda M Hamaguchi |
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Affiliation: | Department of Molecular Pathogenesis, Nagoya University School of Medicine, 65-Tsurumai-cho, Showa-Ku, Nagoya 466, Japan. |
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Abstract: | We found that ectopic expression of N-cadherin in 3Y1 caused tight association of cells and, thereby, substantially suppressed cell growth. N-cadherin expression inhibited neither tyrosine phosphorylation of cellular proteins, GTP uptake onto Ras, nor activation of MAP kinase, suggesting that it does not directly interfere the Ras-MAP kinase pathway. However, co-expression of N-cadherin with dominant negative Ras, S17N Ras, showed synergestic growth inhibitory effect, suggesting that N-cadherin signaling antagonizes the Ras-MAP kinase signaling. In addition, we found that N-cadherin yielded cell-cycle arrest at G0/G1 phase. These results strongly suggest that N-cadherin cell adhesion machinery works as a negative controller of cell cycle in 3Y1 and this growth suppressive function of cadherin is distinct from the epithelial morphogenetic function. |
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