Effect of cellular determination on oncogenic transformation by chemicals and oncogenes.
Three developmentally determined myogenic cell lines derived from C3H 10T1/2 C18 (10T1/2) mouse embryo cells treated with 5-azacytidine were compared with the parental 10T1/2 line for their susceptibility to oncogenic transformation by 3-methylcholanthrene or the activated human c-Ha-ras oncogene. Neither the 10T1/2 cells nor the myogenic derivatives grew in soft agar or formed tumors in nude mice. In contrast to 10T1/2 cells, the three myogenic derivatives were not susceptible to transformation by 3-methylcholanthrene, so that cellular determination altered the response of 10T1/2 cells to chemical carcinogen. On the other hand, all cell types were transformed to a tumorigenic phenotype following transfection with the activated c-Ha-ras gene. The transfected myogenic cells expressed both the c-Ha-ras gene and the muscle determination gene MyoD1. In contrast to other reports, the presence of as many as six copies of the c-Ha-ras gene per genome did not prevent the formation of striated muscle cells which expressed immunologically detectable muscle-specific myosin. The expression of the c-Ha-ras gene does not therefore necessarily preclude the expression of the determination gene for myogenesis or prevent end-stage myogenic differentiation.
Harrington
M A
MA
USC Comprehensive Cancer Center, University of Southern California, Los Angeles 90033.
Gonzales
F
F
Jones
P A
PA
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology* / Q000528:radiation effects; D002472:Cell Transformation, Viral; D019204:GTP-Binding Proteins / Q000235:genetics; D011905:Genes, ras; D008748:Methylcholanthrene / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D009132:Muscles / Q000166:cytology*; D009368:Neoplasm Transplantation; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics
D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D008748:Methylcholanthrene; D019204:GTP-Binding Proteins; D001374:Azacitidine