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Modified responsiveness of v‐Ha‐ ras ‐transfected rat fibroblasts to growth factors and a tumor promoter
Author(s) -
Huang Ming,
Kamata Nobuyuki,
Nose Kiyoshi,
Kuroki Toshio
Publication year - 1988
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.2940010206
Subject(s) - biology , transfection , microbiology and biotechnology , cancer research , gene , genetics
The correlation of the phenotypic changes of v‐Ha‐ ras transfected cells with the expression of p21 ras 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 rastransformed 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 p21 ras protein. Retinoic acid inhibited the TPA‐induced anchorage‐independent growth. These results showed a good correlation of the expression of p21 ras with the phenotypic changes and the increased sensitivity of the p21 ras ‐expressing cells to the stimulation of growth factors and tumor promoter.