Close link between reduction of c-myc expression by interferon and, G0/G1 arrest.
It has recently been reported that c-myc is an inducible gene, regulated directly by growth signals which promote proliferation and expressed in a cell-cycle dependent manner. Because various leukaemic cell lines express high levels of c-myc messenger RNA, it was of interest to discover whether the gene could be down-regulated in these cells by a growth inhibitor such as interferon (IFN). We show here that in Daudi Burkitt's lymphoma cells, IFN-alpha produces a five- to sevenfold reduction in c-myc mRNA through a decreased rate of c-myc gene transcription. By isolating a growth-resistant Daudi cell variant that had escaped from this down-regulation, we provide the first clear link between reduction of c-myc mRNA and the IFN-mediated G0/G1 arrest characteristic of Daudi cells. Furthermore, by screening other cell lines, we demonstrate the heterogeneity of human leukaemic cells with respect to these criteria. Thus, IFN-alpha fails to reduce the c-myc mRNA and to change the cell-cycle distribution in HL-60 and U937 cells, although normal induction of other IFN-regulated activities takes place. The latter group of cells shows a decline in c-myc gene expression when they become arrested in the G0/G1 phase as part of their terminal differentiation.
D015088:2',5'-Oligoadenylate Synthetase / Q000032:analysis; D000818:Animals; D002051:Burkitt Lymphoma; D002454:Cell Differentiation; D002460:Cell Line; D003864:Depression, Chemical; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D007399:Interphase / Q000187:drug effects*; D004915:Leukemia, Erythroblastic, Acute; D015470:Leukemia, Myeloid, Acute; D016403:Lymphoma, Large B-Cell, Diffuse; D051379:Mice; D009857:Oncogenes; D012333:RNA, Messenger / Q000096:biosynthesis
D007370:Interferon Type I; D012333:RNA, Messenger; D015088:2',5'-Oligoadenylate Synthetase