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

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Abstract
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.