Characterization of the superinduction of the c-myc proto-oncogene in fibroblasts by benzamide derivatives.
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.
Devaraj
P E
PE
Division of Immunology, St. George's Hospital Medical School, London, UK.
Clemens
M J
MJ
Johnstone
A P
AP
D016475:3T3 Cells / Q000201:enzymology; D062365:Aminobenzoates / Q000494:pharmacology*; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D014641:Vanillic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D062368:meta-Aminobenzoates
D062365:Aminobenzoates; D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D062368:meta-Aminobenzoates; C025160:3-aminobenzamide; C056267:3-methoxybenzoic acid; C044855:3-aminobenzoic acid; D014641:Vanillic Acid; C025159:3-methoxybenzamide