Mitchell T, Sariban E, Kufe D
Mol Pharmacol. 1986 Oct;30(4):398-402.
We have previously demonstrated that declines in c-myc expression precede the induction of c-fos and c-fms transcripts during monocytic differentiation of human leukemia (HL-60 and U-937) cell lines. The present study has monitored the effects of 1-beta-D-arabinofuranosylcytosine (ara-C) on proto-oncogene expression in U-937 cells. The results demonstrate that ara-C inhibits both U-937 proliferation and c-myc expression in a concentration- and time-dependent manner. At non-toxic concentrations of ara-C, these decreases in c-myc RNA occur in the absence of changes in the level of actin transcripts. The results also demonstrate that ara-C increases c-fos but not c-fms expression. Similar findings have been obtained with retinoic acid. Furthermore, although both agents induce a more mature U-937 phenotype, ara-C is a relatively weak inducer of these cells. These findings would suggest that the changes in proto-oncogene expression induced by ara-C may be related to induction of differentiation or the inhibitory effects of this agent on proliferation.
我们先前已证明，在人白血病（HL-60和U-937）细胞系的单核细胞分化过程中，c-myc表达的下降先于c-fos和c-fms转录本的诱导。本研究监测了1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）对U-937细胞原癌基因表达的影响。结果表明，ara-C以浓度和时间依赖性方式抑制U-937细胞增殖和c-myc表达。在ara-C的无毒浓度下，c-myc RNA的这些减少发生在肌动蛋白转录本水平没有变化的情况下。结果还表明，ara-C增加c-fos表达，但不增加c-fms表达。维甲酸也得到了类似的结果。此外，尽管两种药物都诱导U-937细胞呈现更成熟的表型，但ara-C是这些细胞相对较弱的诱导剂。这些发现表明，ara-C诱导的原癌基因表达变化可能与分化诱导或该药物对增殖的抑制作用有关。
