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.
Jin
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Department of Medical Cell Genetics, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden.
Ringertz
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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