Activation of the proto-oncogene c-myc and c-fos by c-ras: Involvement of polyamines

Rat kidney cells infected with a temperature-sensitive mutant of Kirsten sarcoma virus (Ki-MSV ts 371) expressed Ki-Ras at 37°C but not at 42°C. This expression of the oncogene was accompanied by an increase in the activity of ornithine decarboxylase (ODC) and the accumulation of putrescine. Elevation of cellular polyamine content triggered the transcription of c-myc and c-fos. α-Difluoromethylornithine, a specific inhibitor of ODC, prevented the transcription of c-myc in cells grown at 37°C. Putrescine, at physiological concentrations, triggered the transcription of c-myc and c-fos in cells grown at 42°C, when Ki-ras was not expressed. It has been suggested that polyamines participate in a cascade of events leading to the communication between membrane-bound and nuclear oncogene products. These findings may attribute a new function to the naturally occurring polyamines.