Induction of c-fos but not c-myc in S-91 cells by melanization signals.
Synthesis of the pigment melanin is a complex differentiated function performed by pigment cells in response to a variety of stimuli. The possible roles of the proto-oncogenes c-fos and c-myc in the control of pigmentation were studied using subconfluent, actively proliferating Cloudman S-91 murine melanoma cells stimulated to synthesize melanin by melanocyte stimulating hormone (MSH) or forskolin. Stimulation caused a significant increase in melanin synthesis when compared to control cells, but had no effect on cell growth. Northern analysis of total cellular RNA demonstrated rapid, transient induction of c-fos mRNA as early as 30 min after stimulation with MSH or forskolin. In contrast, there was no effect on the high constitutive expression of c-myc in these actively proliferating cells. These data strongly suggest that the induction of c-fos mRNA is an early genetic event in stimulation of melanin synthesis and thus this proto-oncogene may play a major role in the regulation of this differentiated function, as reported for other forms of cellular differentiation. In contrast, c-myc expression is unaffected and instead correlated with cellular proliferative capacity. These results are consistent with the hypothesis that the down-regulation of c-myc frequently observed during cell differentiation is not a necessary event, but rather reflects an associated decrease in cell growth rate. The S-91 melanoma system appears to provide a convenient model for study of the regulation for a single, well defined differentiated function that is independent of growth rate.
Gordon
L
L
Department of Dermatology, Boston University School of Medicine, MA 02118.
Peacocke
M
M
Gilchrest
B A
BA
D000818:Animals; D001345:Autoradiography; D015152:Blotting, Northern; D002452:Cell Count; D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D005576:Colforsin / Q000494:pharmacology; D015342:DNA Probes; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D008543:Melanins / Q000032:analysis / Q000378:metabolism / Q000502:physiology*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D008546:Melanoma, Experimental / Q000737:chemistry / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000473:pathology
D015342:DNA Probes; D008543:Melanins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D005576:Colforsin; D009074:Melanocyte-Stimulating Hormones