Reactivation of ribosomal RNA genes in human-mouse hybrid cells by 12-O-tetradecanoylphorbol 13-acetate.

The effect of the potent tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) on the expression of rRNA genes was studied in human greater than mouse hybrid cells (55-54 cells). These hybrids retain the rRNA genes of both parent species but express only human rRNA. 55-54 cells were treated with either TPA (1-100 nM), phorbol (0.01-1 micro M) or phorbol 13,20-diacetate (0.01-1 micro M). After 24 hr the cells were harvested and the extracted rRNA was analyzed by agarose/2.4% polyacrylamide gel electrophoresis. The results show that only the TPA-treated hybrid cells synthesized both human and mouse 28S rRNA. Untreated cells and cells treated with phorbol or phorbol 13,20-diacetate synthesized only human 28S rRNA. The reactivation of silent rRNA genes by TPA was not restricted to mouse rRNA genes. In mouse-human hybrids in which both human and mouse rRNA genes are present but only the mouse genes are expressed, TPA treatment led to reactivation of the silent human rRNA genes. Although tumor promoters are generally believed to alter gene expression, we have found a specific gene whose transcription is modified by treatment with TPA.