Plettenberg A, Ballaun C, Pammer J, Mildner M, Strunk D, Weninger W, Tschachler E
Department of Dermatology, University of Vienna Medical School, Austria.
Am J Pathol. 1995 Mar;146(3):651-9.
The Bcl-2 proto-oncogene regulates cell survival by antagonizing events that lead to apoptotic cell death and has been reported to be expressed in situ in lymphoid tissues, glandular epithelium, neurons, and basal epidermal cells. When we performed immunostaining on cryostat sections of normal skin, anti-Bcl-2 reactivity was confined to scattered dendritic cells in the basal epidermal layer. Double-staining experiments showed that the Bcl-2+ cells were positive for vimentin but negative for cytokeratins, CD1a, and CD45 antigens, excluding keratinocytes and Langerhans cells as possible candidates for constitutive Bcl-2 expression. Bcl-2+ epidermal cells also reacted with the monoclonal anti-melanocyte antibody NKI/beteb, and were absent from lesional skin in vitiligo, confirming that they represented epidermal melanocytes. Western blot analysis of cultured melanocytes and melanoma cell lines revealed a 26-kd protein specifically reacting with the anti-Bcl-2 monoclonal antibody. Immunostaining of pigmented lesions revealed strong expression of Bcl-2 by five of five nevocellular nevi and seven of seven melanomas. Our observations demonstrate that, within normal human epidermis, melanocytes are the only cells that express Bcl-2 constitutively and that Bcl-2 is expressed in benign and malignant pigmented tumors of the skin in situ.
Bcl-2原癌基因通过拮抗导致凋亡性细胞死亡的事件来调节细胞存活，且据报道其在淋巴组织、腺上皮、神经元和基底表皮细胞中可原位表达。当我们对正常皮肤的冷冻切片进行免疫染色时，抗Bcl-2反应仅限于基底表皮层中散在的树突状细胞。双重染色实验表明，Bcl-2阳性细胞波形蛋白呈阳性，但细胞角蛋白、CD1a和CD45抗原呈阴性，排除了角质形成细胞和朗格汉斯细胞作为Bcl-2组成性表达的可能候选细胞。Bcl-2阳性表皮细胞也与抗黑素细胞单克隆抗体NKI/beteb发生反应，且在白癜风的皮损中不存在，证实它们代表表皮黑素细胞。对培养的黑素细胞和黑色素瘤细胞系进行的蛋白质印迹分析显示，一种26kd的蛋白能与抗Bcl-2单克隆抗体特异性反应。色素性皮损的免疫染色显示，5例痣细胞痣和7例黑色素瘤中有5例和7例Bcl-2呈强表达。我们的观察结果表明，在正常人类表皮内，黑素细胞是唯一组成性表达Bcl-2的细胞，且Bcl-2在皮肤的良性和恶性色素性肿瘤中可原位表达。
