Selective inhibition of c-myc expression by the ribonucleic acid synthesis inhibitor mithramycin.
Expression of the c-myc proto-oncogene has been shown to correlate with the rate of cellular proliferation and malignant transformation in a number of cell types. JEG-3 choriocarcinoma cells demonstrate c-myc transcript levels that are greater than those of nonmalignant trophoblastic tissue at any stage of gestation. Southern blot analysis documents c-myc gene amplification in JEG-3 cells, with a gene copy number of approximately 20. The methylation pattern and genomic structure of the amplified c-myc oncogene in JEG-3 choriocarcinoma cells are identical to those of normal placenta. Treatment of JEG-3 cells with mithramycin, a ribonucleic acid synthesis inhibitor, results in a dramatic decrease in c-myc expression relative to that of the c-Ha-Ras gene. The apparent selectivity of mithramycin for c-myc expression represents the only example, to date, of the selective pharmacologic modulation of oncogene expression.
Baker
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VV
Department of Internal Medicine, University of Alabama, Birmingham 35294.
Shingleton
H M
HM
Hatch
K D
KD
Miller
D M
DM
D002460:Cell Line; D002822:Choriocarcinoma / Q000188:drug therapy / Q000235:genetics*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects; D005821:Genetic Techniques; D005865:Gestational Age; D006801:Humans; D010920:Placenta; D008926:Plicamycin / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D000090063:Proto-Oncogene Mas; D011519:Proto-Oncogenes / Q000187:drug effects*; D014594:Uterine Neoplasms / Q000188:drug therapy / Q000235:genetics*
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D008926:Plicamycin