Similarities and differences in the regulation of N-myc and c-myc genes in murine embryonal carcinoma cells.

c-myc and N-myc are closely related genes coding for putative DNA-binding proteins. The protein products of both genes have been implicated in the regulation of growth of normal and neoplastic cells. We compared the regulation of N-myc and c-myc expression under different growth conditions as well as in vitro differentiation of the murine EC lines F9 and PCC7. N-myc and c-myc expression was found to be regulated by distinct mechanisms, although similarities exist. Differences were found both at the transcriptional and at the post-transcriptional level. The two myc genes were regulated by mainly post-transcriptional mechanisms, but in PCC7 cells nuclear run-on assays indicated that c-myc was repressed at the level of transcription. N-myc and c-myc expression was negatively regulated at a post-transcriptional level in F9 and PCC7 cells during differentiation to visceral endoderm and nerve-like tissue, respectively. Serum stimulation of F9 cells for 4 h induced a sevenfold increase in c-myc transcripts but no significant elevation of N-myc transcripts. Mitogenic stimulation with insulin and transferrin also induced a marked elevation of c-myc but not of N-myc mRNA. In addition, the N-myc and c-myc genes differed in F9 cells with respect to (i) the kinetics of expression following induction of differentiation, c-myc undergoing quicker changes than N-myc; (ii) the response to cycloheximide inhibition of protein synthesis, indicating that c-myc but not N-myc is down-regulated by a short-lived protein; and (iii) the half-lives of the transcripts, estimated to be approximately 40 min for c-myc and 130 min for N-myc.