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Characterization of the superinduction of the c-myc proto-oncogene in fibroblasts by benzamide derivatives

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Abstract

In mouse fibroblasts stimulated from quiescence into proliferation by serum the induction of expression of the c-myc proto-oncogene is strongly stimulated by 3-methoxybenzamide. Similar superinduction effects are seen with related compounds such as 3-aminobenzamide and the acid analogues, 3-anisic acid and 3-aminobenzoic acid. Whereas the benzamide derivatives are inhibitors of poly(ADP-ribose) polymerase the acid analogues are not, suggesting that inhibition of this enzyme is not the basis for superinduction of the c-myc gene. Analysis of the kinetics of induction of c-myc mRNA indicates that the RNA accumulates more rapidly as well as to a higher level in the presence of serum plus 3-methoxybenzamide than with serum alone. However the stimulation is transient in both cases. Addition of actinomycin D at 30 min or 1 h after serum stimulation shows the c-myc mRNA to be stable at these times, in the presence or absence of 3-methoxybenzamide. Thus the effect of the latter on c-myc mRNA accumulation is likely to be exerted at the level of transcription or RNA processing rather than turnover of the mRNA.

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Devaraj, P.E., Clemens, M.J. & Johnstone, A.P. Characterization of the superinduction of the c-myc proto-oncogene in fibroblasts by benzamide derivatives. Mol Cell Biochem 124, 175–181 (1993). https://doi.org/10.1007/BF00929210

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  • DOI: https://doi.org/10.1007/BF00929210

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