Cadmium induces transcription of proto-oncogenes c-jun and c-myc in rat L6 myoblasts.
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.
Department of Medical Cell Genetics, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
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D000818:Animals; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D009132:Muscles; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000235:genetics* / Q000302:isolation & purification; D051381:Rats; D015183:Restriction Mapping; D014157:Transcription Factors / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D014157:Transcription Factors; D002104:Cadmium; D012313:RNA; D011505:Protein-Tyrosine Kinases; D019256:Cadmium Chloride