Gordon L, Peacocke M, Gilchrest B A
Department of Dermatology, Boston University School of Medicine, MA 02118.
J Dermatol Sci. 1992 Jan;3(1):35-41. doi: 10.1016/0923-1811(92)90006-w.
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.
色素黑色素的合成是色素细胞响应多种刺激而执行的一种复杂的分化功能。利用亚汇合的、活跃增殖的Cloudman S - 91小鼠黑色素瘤细胞，研究原癌基因c - fos和c - myc在色素沉着控制中的可能作用。这些细胞通过黑素细胞刺激激素（MSH）或福斯高林刺激来合成黑色素。与对照细胞相比，刺激导致黑色素合成显著增加，但对细胞生长没有影响。对总细胞RNA的Northern分析表明，在用MSH或福斯高林刺激后早在30分钟，c - fos mRNA就有快速、短暂的诱导。相反，对这些活跃增殖细胞中c - myc的高组成型表达没有影响。这些数据强烈表明，c - fos mRNA的诱导是刺激黑色素合成过程中的一个早期遗传事件，因此，正如在其他形式的细胞分化中所报道的那样，这个原癌基因可能在这种分化功能的调节中起主要作用。相比之下，c - myc的表达不受影响，而是与细胞增殖能力相关。这些结果与以下假设一致，即在细胞分化过程中经常观察到的c - myc下调不是一个必要事件，而是反映了细胞生长速率的相关降低。S - 91黑色素瘤系统似乎为研究一种独立于生长速率的单一、明确的分化功能的调节提供了一个便利的模型。
