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.
Sejersen
T
T
Department of Medical Cell Genetics, Karolinska Institutet, Stockholm, Sweden.
Rahm
M
M
Szabo
G
G
Ingvarsson
S
S
Sümegi
J
J
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004707:Endoderm; D005786:Gene Expression Regulation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009474:Neurons; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc; D011519:Proto-Oncogenes; D013724:Teratoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014168:Transferrin / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000378:metabolism*
D007328:Insulin; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D014168:Transferrin; D003513:Cycloheximide