Jin P, Ringertz N R
Department of Medical Cell Genetics, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
J Biol Chem. 1990 Aug 25;265(24):14061-4.
The effect of cadmium on the expression of oncogenes c-jun, c-fos, and c-myc was studied by exposing L6J1 myoblast cultures to different doses of cadmium chloride and then analyzing the abundance of oncogene transcripts. Cadmium induced a transient accumulation of c-jun and c-myc mRNA with maximum expression at 2-4 h. At the same time, the level of c-fos transcripts remained below the detection level. Both the c-fos and c-jun genes could. However, be induced by treating the myoblasts with insulin. Cadmium induction of c-jun and c-myc mRNA occurred in a concentration-dependent manner with maximum stimulation at 5-10 microM. In the presence of cycloheximide, c-jun and c-myc genes were superinduced by the addition of cadmium. Under these conditions there was also a marked increase in c-fos transcripts. Induction of c-myc and c-jun by cadmium and c-fos by a combination of cadmium and cycloheximide could be abolished by blocking transcription with actinomycin D. The cadmium-induced increase in c-jun and c-myc mRNA was enhanced in myoblasts stably transfected with a mouse c-fos gene under a metallothionein promoter. Our present data suggest that cadmium has the potential to deregulate the expression of several important oncogenes.
通过将L6J1成肌细胞培养物暴露于不同剂量的氯化镉，然后分析癌基因转录本的丰度，研究了镉对癌基因c-jun、c-fos和c-myc表达的影响。镉诱导c-jun和c-myc mRNA短暂积累，在2-4小时达到最大表达。与此同时，c-fos转录本水平仍低于检测水平。然而，c-fos和c-jun基因都可以通过用胰岛素处理成肌细胞来诱导。镉对c-jun和c-myc mRNA的诱导呈浓度依赖性，在5-10 microM时刺激最大。在存在环己酰亚胺的情况下，添加镉会使c-jun和c-myc基因超诱导。在这些条件下，c-fos转录本也有显著增加。用放线菌素D阻断转录可消除镉对c-myc和c-jun的诱导以及镉和环己酰亚胺组合对c-fos的诱导。在金属硫蛋白启动子下稳定转染小鼠c-fos基因的成肌细胞中，镉诱导的c-jun和c-myc mRNA增加增强。我们目前的数据表明，镉有可能失调几种重要癌基因的表达。
