ABSTRACT
The process of cell differentiation in Friend-erythroleukemia cells was accompanied by 80-90% inhibition of p53 synthesis. This decrease was found to be linked to changes in cell-cycle distribution characteristics of the growth arrest program during differentiation rather than to the induction of the globin genes. The shut-off in the expression of p53 always preceded the specific arrest of cells in the G0/G1 phase. Interferon did not modulate down the expression of p53 if added to transformed non-induced Friend-erythroleukemia cells; however, it slightly enhanced the extent of reduction in p53 synthesis if added during cell differentiation, thus suggesting a differential effect of interferon between cells at different stages of differentiation.
Subject(s)
Leukemia, Erythroblastic, Acute/metabolism , Leukemia, Experimental/metabolism , Phosphoproteins/biosynthesis , Animals , Cell Division/drug effects , Cell Transformation, Neoplastic , Cells, Cultured , Friend murine leukemia virus , Interferon Type I/pharmacology , Mice , Tumor Suppressor Protein p53ABSTRACT
We have examined the relationship between induction of interferon (IFN) and prostaglandin E (PGE) production by poly(rI).poly(rC) in cultured human foreskin fibroblasts (FS11). Hydrocortisone and dexamethasone (2 . 5 x 10(-7) M), which are known inhibitors of PGE synthesis, significantly decreased the induction of both IFN and PGE in IFN-pretreated (primed) cells. Desoxycorticosterone, progesterone and estradiol were devoid of this activity. Hydrocortisone also blocked the induction of IFN by double-stranded RNA (dsRNA), cycloheximide and actinomycin D in FS11 cells. Arachidonic acid overcame the inhibitory effect of hydrocortisone on PGE production, but failed to restore IFN production in the presence of the steroid. Moreover, the prostaglandin synthetase inhibitors, indomethacin, aspirin and flufenamic acid, did not change IFN production by dsRNA in primed FS11 cells, although prostaglandin synthesis was abolished. Although the induction of IFN and PGE by poly(rI).poly(rC) might be consequences of the same initial event in the cell, the accumulation of PGE does not seem to have a regulatory effect on the synthesis of IFN in this system.
