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-molecular-weight tropomyosin (TM) expression in growth factor- and various oncogene-induced transformation was studied by using NRK cells and its transformation-deficient mutants. In NRK cells which show a transformed phenotype by treatment with EGF and TGF-beta, cellular stress fibers became dissociated by EGF or EGF and TGF-beta combination, whereas TGF-beta alone caused thicker appearance of stress fibers. Accompanying these changes, the expression of TM isoforms 1 and 2 was suppressed by treatment with EGF or EGF and TGF-beta, but elevated by TGF-beta with similar time courses. On the other hand, the transformation-deficient mutant cell lines, 39-1 and 39-3, did not show the transformed phenotypes 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 the formation of stress fibers and the expression of TM isoforms was consistent in NRK cells, the mutant lines and their various oncogene-expressing sublines under various culture conditions. NRK cells overexpressing exogenous mouse TM isoform 2 showed markedly decreased susceptibility to EGF-induced dissociation of stress fibers and decreased anchorage-independent growth potential in the presence of EGF and TGF-beta. These results indicate that the transformation-deficient NRK mutant lines, 39-1 and 39-3 have defects in an EGF signal transduction pathway which induces suppression of high-molecular-weight TM expression and disassembly of microfilament bundles and suggested that the activation of the pathway is important for morphological transformation and oncogenic growth in growth factors- and various oncogene-induced transformation of NRK cells.
Masuda
A
A
Laboratory of Ultrastructure Research, Aichi Cancer Research Institute, Nagoya, Japan.
Takenaga
K
K
Kondoh
F
F
Fukami
H
H
Utsumi
K
K
Okayama
H
H
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression; D007536:Isomerism; D051379:Mice; D009154:Mutation; D009857:Oncogenes; D015398:Signal Transduction / Q000502:physiology*; D014335:Tropomyosin / Q000096:biosynthesis* / Q000235:genetics
D000199:Actins; D014335:Tropomyosin; D004815:Epidermal Growth Factor