Modulation of Globin Gene Expression by a Tumor Promoter during Induced Differentiation of Friend Erythroleukemic Cells

Abstract

Friend erythroleukemic cells were induced to differentiate by dimethylsulfoxide (Me2SO) in the absence or presence of the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate. The effects of the latter on the molecular parameters related to globin mRNA metabolism were examined. When differentiation was scored by benzidine staining, the tumor promoter was shown to have an inhibitory effect on Me2SO-treated cells. When differentiation was followed by determination of globin mRNA accumulation, tumor promoter treatment was shown to have a pleiotropic effect on Me2SO-treated cells. At the early phase of differentiation (2-3 days), the rate of globin mRNA accumulation was higher in the promoter-treated cells than in the control. This unexpectedly high level of accumulation was followed by a sharp reduction and most of the globin RNA sequences disappeared at later stages of differentiation (days 4-5). The reduction can be related to the effect of the promoter on the stability of globin RNA in the cytoplasm which was reduced from a half-life of 16 h to 8 h. Other parameters, such as the rate of globin mRNA synthesis and its capability to serve as a template for cell-free protein synthesis, were not affected by treatment with the promoter throughout the differentiation process.