Sermadiras S, Dumas M, Joly-Berville R, Bonté F, Meybeck A, Ratinaud M H
Parfums Christian Dior, Saint Jean de Braye, France.
Br J Dermatol. 1997 Dec;137(6):883-9.
Keratinocyte differentiation and melanogenesis are two major cellular processes by which the epidermal compartment of the skin acquires its protective properties. Bcl-2; an oncoprotein involved in the regulation of apoptosis, has been shown to be expressed by keratinocytes and melanocytes. To determine whether Bcl-2 and Bax, a protein which heterodimerizes with Bcl-2, may control these epidermal functions, we investigated the expression of these two oncogenes in cultivated human keratinocytes and melanocytes from the same donors, respectively induced to differentiate and to produce melanin. As determined by cytometry, we observed that these two cell types constitutively express the two proto-oncogenes. Quantification of Bcl-2 antigen sites per cell showed that Bcl-2 expression is higher in keratinocytes than in melanocytes. An increase in transglutaminase activity, a marker of keratinocyte terminal differentiation initiating cornified envelope formation, was accompanied by a decrease in Bcl-2 levels without significant modification of Bax expression. In melanocyte cultures, stimulation of the dopa-oxidase pool, a key enzyme in melanin synthesis, paralleled Bcl-2 down-regulation and Bax up-regulation. This led us to conclude that the expression of these two oncogenes and their cellular ratio are closely involved in keratinocyte differentiation and melanogenesis.
角质形成细胞分化和黑素生成是皮肤表皮部分获得其保护特性的两个主要细胞过程。Bcl-2是一种参与细胞凋亡调节的癌蛋白，已被证明可由角质形成细胞和黑素细胞表达。为了确定Bcl-2和与Bcl-2形成异二聚体的蛋白Bax是否可能控制这些表皮功能，我们分别研究了来自相同供体的培养人角质形成细胞和黑素细胞中这两种癌基因的表达，这些细胞分别被诱导分化和产生黑色素。通过细胞计数法测定，我们观察到这两种细胞类型组成性地表达这两种原癌基因。每个细胞Bcl-2抗原位点的定量分析表明，角质形成细胞中Bcl-2的表达高于黑素细胞。转谷氨酰胺酶活性增加，这是角质形成细胞终末分化启动角质包膜形成的标志物，同时伴随着Bcl-2水平的降低，而Bax表达没有明显改变。在黑素细胞培养物中，黑色素合成关键酶多巴氧化酶池的刺激与Bcl-2下调和Bax上调平行。这使我们得出结论，这两种癌基因的表达及其细胞比例密切参与角质形成细胞分化和黑素生成。
