Phorbol ester induces the transcriptional stimulatory activity of the SV40 enhancer

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Abstract
Phorbol ester tumour promoters can induce the transcription of a number of genes1, including c-myc and c-fos2. These genes are part of a group referred to as ‘competence’ genes3,4 because they are expressed very early after quiescent cells are stimulated to enter the cell cycle5–7. The ‘competence’ genes are coordinately induced by serum and by factors such as platelet-derived growth factor and fibroblast growth factor1,2,8–12. These factors, as well as the tumour promoter, 12-O-tetradecanoyl phorbol-13-acetate (TPA), are thought to exert their action by a mechanism involving the activation of protein kinase C13–16. It is likely that these factors induce the transcription of the ‘competence’ genes either by activating specific transcription factors or by increasing their intracellular concentration; either mechanism may be mediated by protein kinase C. One approach to identifying such a putative transcription factor is to characterize the cis-acting transcriptional control elements that serve as a target site for the factor. Here we report that, in a human hepatoma cell line, TPA can specifically induce the activity of the simian virus 40 (SV40) transcriptional enhancer element. Since the SV40 enhancer is a thoroughly characterized cis-actitng element17–19, this system may facilitate the eventual identification of the trans-acting factor(s) whose activity is modified by TPA treatment.