Stimulation of c-myc protooncogene expression by transforming growth factor a in human ovarian cancer cells

Abstract

To investigate whether transforming growth factor α (TGF α) treatment of human ovarian cancer cells was associated with the induction of c-myc protooncogene, the expression of this gene in NIH:OVCAR-3 cells was examined. TGF α induced increase in c-myc mRNA level, with a peak after 1 h of treatment; this stimulation was dose-dependent, with an optimal concentration of 5 ng/ml TGF α. Its primary action is probably at the transcription level since the half-life of c-myc mRNA measured in the presence of actinomycin D was not modified by TGF α treatment. In addition, TGF α stimulation of c-myc mRNA did not require protein synthesis since it was not suppressed by cycloheximide treatment. Antisense phosphorothioate oligonucleotide to c-myc specifically inhibited the TGF α-stimulated c-Myc protein expression and growth of NIH:OVCAR-3 cells. Our results indicate that induction of c-myc expression by TGF α plays an important role in the growth of NIH:OVCAR-3 cells.