ROLE OF A SIGNAL-TRANSDUCTION PATHWAY WHICH CONTROLS DISASSEMBLY OF MICROFILAMENT BUNDLES AND SUPPRESSION OF HIGH-MOLECULAR-WEIGHT TROPOMYOSIN EXPRESSION IN ONCOGENIC TRANSFORMATION OF NRK CELLS

Role of disassembly of microfilament bundles and suppression of high-m olecular-weight tropomyosin (TM) expression in growth factor- and vari ous oncogene-induced transformation was studied by using NRK cells and its transformation-deficient mutants. In NRK cells which show a trans formed phenotype by treatment with EGF and TGF-beta, cellular stress f ibers became dissociated by EGF or EGF and TGF-beta combination, where as TGF-beta alone caused thicker appearance of stress fibers, Accompan ying these changes, the expression of TM isoforms 1 and 2 was suppress ed by treatment with EGF or EGF and TGF-beta, but elevated by TGF-beta with similar time courses, On the other hand, the transformation-defi cient mutant cell Lines, 39-1 and 39-3, did not show the transformed p henotypes by treatment with EGF and TGF-beta. Neither EGF nor EGF and TGF-beta combination affected cellular stress fibers and expression of TM isoforms 1 and 2 in both mutant lines, The relationship between th e formation of stress fibers and the expression of TM isoforms was con sistent in NRK cells, the mutant lines and their various oncogene-expr essing sublines under various culture conditions, NRK cells overexpres sing exogenous mouse TM isoform 2 showed markedly decreased susceptibi lity to EGF-induced dissociation of stress fibers and decreased anchor age-independent growth potential in the presence of EGF and TGF-beta. These results indicate that the transformation-deficient NRK mutant li nes, 39-1 and 39-3 have defects in an EGF signal transduction pathway which induces suppression of high-molecular-weight TM expression and d isassembly of microfilament bundles and suggested that the activation of the pathway is important for morphological transformation and oncog enic growth in growth factors- and various oncogene-induced transforma tion of NRK cells.