S-adenosylmethionine decarboxylase gene expression in rat hepatoma cells: regulation by insulin and by inhibition of protein synthesis.

We have investigated expression of the S-adenosylmethionine decarboxylase (AdoMetDC) gene in H4-II-E rat hepatoma cells treated with growth factors (epidermal growth factor and transforming growth factor beta 1) and inducers (cAMP and insulin). Treatment with insulin caused a marked increase in both RNA level and enzyme activity. The stability of AdoMetDC mRNA was not altered by insulin treatment: the accumulation of mRNA in hepatoma cells therefore seems to be due to an increase in the transcription rate. Cycloheximide was found to be a strong inducer of AdoMetDC mRNA transcription and the effects of insulin and cycloheximide were additive, suggesting that they increase expression by separate mechanisms. Chloramphenicol acetyltransferase assays in rat hepatoma cells using 5' flanking regions of different lengths revealed that the promoter region extending 337 bp upstream from the transcription start site contains elements involved in insulin response.