Kinetics of cellular oncogene expression in mouse lymphocytes. II. Regulation of c-fos and c-myc gene expression.

Newly isolated lymphocytes from mouse spleens express the c-fos oncogene even in the absence of mitogen with maximal mRNA levels 60 min post preparation of single cell suspension, whereas c-myc mRNA levels increase only after mitogenic stimulation with maximal mRNA levels 6 h post stimulation. The half-lives of c-fos mRNA are generally very short; they increase from 14 min (after 30 min of culture) to 70 min (after 2 h of culture). The half-lives of c-myc mRNA decrease from 50 min (at 2 and 6 h post stimulation with concanavalin A) to 12 min (at 48 h post stimulation). The c-fos gene transcription is already turned on in time-0 lymphocytes 10 min after disruption of the organ structure of the spleens and is down-regulated after 2 h and later. In nuclear run-on experiments with nonstimulated lymphocytes there is already significant transcription of the first exon of c-myc, but almost no elongation of the transcript to exon 2 and 3. In concanavalin A-treated lymphocytes elongation is stimulated about 5-fold within 6 h and returns to background levels at 48 h post stimulation. The nuclear run-on analyses of nonactivated lymphocytes showed a signal for RNA complementary to c-myc mRNA detected with a probe specific for the exon 1/intron 1 boundary of c-myc, which disappeared with increasing time of concanavalin A stimulation. This anti-sense transcription may play a role in regulating the elongation of c-myc transcripts.