Transient induction of ornithine decarboxylase mRNA in rat hepatoma cells treated with 12-O-tetradecanoylphorbol-13-acetate.

The contribution of changes in mRNA levels to the induction of ornithine decarboxylase (ODC) by 12-O-tetradecanoylphorbol-13-acetate (TPA) in rat H35 hepatoma cells was analyzed by Northern blot and quantitative dot blot hybridization. ODC mRNA accumulated rapidly in TPA-treated cultures. The increase in message was transient, reaching a peak within about 3 h, then declining to control levels after 18 h. Maximal accumulation of ODC-specific mRNA varied from 3- to 8-fold above control. The TPA dose-response for ODC message accumulation was half-maximal at approximately 0.18 microM TPA. The increase was completely blocked by actinomycin D, suggesting that TPA stimulates the transcription of ODC genes. Inhibition of protein synthesis by cycloheximide (10 micrograms/ml) led to a superinduction of ODC mRNA in the presence of TPA, which suggested that a short-lived protein may be responsible for negative control of ODC expression.