ACTIVATION OF THE PROTOONCOGENE C-MYC AND C-FOS BY C-RAS - INVOLVEMENT OF POLYAMINES

Rat kidney cells infected with a temperature-sensitive mutant of Kirst en sarcoma virus (Ki-MSV ts 371) expressed Ki-Ras at 37 degrees C but not at 42 degrees C. This expression of the oncogene was accompanied b y an increase in the activity of ornithine decarboxylase (ODC) and the accumulation of putrescine. Elevation of cellular polyamine content t riggered the transcription of c-myc and c-fos. alpha-Difluoromethylorn ithine, a specific inhibitor of ODC, prevented the transcription of c- myc in cells grown at 37 degrees C. Putrescine, at physiological conce ntrations, triggered the transcription of c-myc and c-fos in cells gro wn at 42 degrees C, when Ki-ras was not expressed. It has been suggest ed that polyamines participate in a cascade of events leading to the c ommunication between membrane-bound and nuclear oncogene products. The se findings may attribute a new function to the naturally occurring po lyamines. (C) 1994 Academic Press, Inc.