Growth stimulation of rat primary embryo fibroblasts by the human myc gene.
We have studied the ability of plasmids encoding a normal human myc protein to stimulate growth of primary rat embryo fibroblasts. We measured growth stimulation by the number of G418-resistant colonies obtained after co-transfection with plasmid pSV2neo and by the percentage of these colonies that grew in long-term culture (immortalization). Using a normal human myc gene, we detected a weak growth stimulation at the colony formation stage and a low frequency of immortalization. Replacement of the myc promoter by a heterologous promoter (mouse metallothionein I promoter) and deletion of the first non-coding exon led to a more efficient growth stimulation by both criteria. Thus, disregulation of c-myc is essential for an altered pattern of growth. Using zinc, a metallothionein inducer, we observed a slight increase in the growth rate of some transfectants, which can be measured by thymidine incorporation. However, the relative inefficiency of immortalization we observed suggests that either a high level of myc expression or participation of other genes is required for establishment in culture. Under our experimental conditions, we could not detect a transforming activity for the human myc gene and none of our myc-containing cell lines was tumorigenic in nude mice.
D000818:Animals; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D002999:Clone Cells; D005347:Fibroblasts; D006801:Humans; D051379:Mice; D009857:Oncogenes; D011401:Promoter Regions, Genetic; D051381:Rats; D014158:Transcription, Genetic; D014162:Transfection