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Effects of various chemical agents on the transformation of rat fibroblasts by an activated c‐Ha‐ ras oncogene
Author(s) -
Lopez Cecilia A.,
Hsiao W.L. Wendy,
Weinstein I. Bernard
Publication year - 1989
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.2940020206
Subject(s) - biology , oncogene , microbiology and biotechnology , biochemistry , epidermal growth factor , transfection , retinoic acid , cell culture , cell , cell cycle , receptor , genetics , gene
We have previously reported that the potent tumor‐promoting agent 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) and a factor from fetal calf serum (FCS) markedly enhance the transformation of mouse C3H 10T1/2 and Rat 6 fibroblasts, when added to cultures following transfection with plasmid pT24 DNA that contains an activated c‐Ha‐ras oncogene. In the present study, we examined possible enhancing or inhibiting effects of various chemicals on the transformation of Rat 6 fitbroblasts by T24 DNA when tested in the presence of calf serum, calf serum plus TPA or FCS. We found that, like TPA, the chemicals mezerein, 1‐oleoyl‐2‐acetylglycerol, and phospholipase C increased the yield of T24‐induced foci, thus further implicating protein kinase C as a critical constituent in this process. Low concentrations (10 −6 –10 −7 M) of retinoic acid (both trans and 13‐ cis ) also stimulated cell transformation. Several compounds inhibited T24‐induced transformation. These included nontoxic concentrations of the calcium ionophore A23187, indomethacin, and ϵ‐amino‐ n ‐caproic acid. Compounds that failed to exert a significant reproducible effect included vasopressin, vitamin D 3 , selenium, antipain, Bowman‐Birk inhibitor, vitamin B 12 , epidermal growth factor, platelet‐derived growth factor, insulin, and transferrin. These findings suggest that this simple in vitro system might be useful for detecting enhancers and inhibitors of ras oncogene‐induced cell transformation and also elucidating their mechanisms of action.