Modified responsiveness of v-Ha-ras-transfected rat fibroblasts to growth factors and a tumor promoter.
The correlation of the phenotypic changes of v-Ha-ras transfected cells with the expression of p21ras and the modified responses to growth factors and a tumor promoter were examined. Transfection of the v-Ha-ras gene together with the neomycin-resistance gene into 208F rat fibroblasts yielded transformed clones characterized by morphological changes, anchorage-independent growth, and tumorigenicity in nude mice. The degrees of these biological alterations were parallel with the expression of mRNA and protein of the ras gene. In ras-transformed cells, anchorage-independent growth was stimulated by epidermal growth factor (EGF), insulin, bombesin, and fibroblast growth factor, whereas in the parental 208F cells, anchorage-independent growth was observed only in the presence of EGF, and there were many fewer EGF-induced colonies than those in the ras-transformed clones. A tumor promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA) also augmented anchorage-independent growth of ras-transformed cells and induced morphological changes in monolayer cultures without altering the expression of the ras gene or phosphorylation of the p21ras protein. Retinoic acid inhibited the TPA-induced anchorage-independent growth. These results showed a good correlation of the expression of p21ras with the phenotypic changes and the increased sensitivity of the p21ras-expressing cells to the stimulation of growth factors and tumor promoter.
Huang
M
M
Department of Cancer Cell Research, University of Tokyo, Japan.
Kamata
N
N
Nose
K
K
Kuroki
T
T
D000818:Animals; D015152:Blotting, Northern; D001839:Bombesin / Q000494:pharmacology; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000494:pharmacology*; D002448:Cell Adhesion; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009857:Oncogenes; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014162:Transfection
D002273:Carcinogens; D011518:Proto-Oncogene Proteins; D004815:Epidermal Growth Factor; D016283:Proto-Oncogene Proteins p21(ras); D013755:Tetradecanoylphorbol Acetate; D001839:Bombesin