Development of cutaneous amelanotic melanoma in the absence of a functional tyrosinase.
Development of cutaneous amelanotic melanoma in the absence of a functional tyrosinase.
复制标题
在缺乏功能性酪氨酸酶的情况下皮肤无色素性黑色素瘤的发展。
DOI：
10.1034/j.1600-0749.2001.140607.x
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Chen,S
中科院分区：
文献类型：
--
作者：
Cohen-Solal,KA;Reuhl,KR;Ryan,KB;Roberts,KG;Chen,S
缺乏特征性色素沉着和广泛的临床表现是与无色素性恶性黑色素瘤相关的诊断挑战。由于缺乏适当的动物模型，对这种重要的人类癌症的实验研究受到阻碍。我们先前描述了一种自发发展色素性皮肤黑色素瘤的转基因小鼠系（TG-3）。用TG-3和几种白化病菌株产生F1杂交，然后用白化病菌株进行回交。在本报告中，我们描述了这些白化病转基因回交的皮肤无黑色素性黑色素瘤的限制发展和特点。监测这些小鼠中黑素瘤的发病率和行为。在与A、AKR、FVB和SJL品系回交的白化病转基因小鼠中观察到自发性无黑色素性黑素瘤的高发病率（80-100%）。在BALB/c衍生杂交中获得的发生率最低（30%）。在非转基因小鼠中未观察到肿瘤。使用针对酪氨酸酶蛋白家族的三种黑素细胞特异性标志物的抗体进行免疫组织化学和蛋白质印迹分析，证实肿瘤由无色素黑素细胞组成。此外，通过电子显微镜观察到的大量前黑素体的存在进一步支持了这些肿瘤的黑素细胞起源。先前关于人黑色素瘤的体外研究表明，皮肤无色素性黑色素瘤是从既存色素性皮肤黑色素瘤演变而来的。然而，我们的研究结果表明，它可以直接发生，如酪氨酸酶缺陷白化病小鼠皮肤无色素性黑色素瘤的出现所证明的。这些小鼠代表了研究这种高度恶性肿瘤的机制、诊断和治疗特征的潜在有价值的模型。
Lack of characteristic pigmentation and a wide range of clinical presentations account for the diagnostic challenge associated with amelanotic malignant melanoma. Experimental studies of this important human cancer have been hampered by the lack of an appropriate animal model. We previously described a transgenic mouse line (TG‐3) that spontaneously develops pigmented cutaneous melanoma. F1 crosses were generated with TG‐3 and several albino strains, and backcrosses were then made with the albinos. In the present report, we describe the restricted development and characterization of cutaneous amelanotic melanoma in these albino transgenic backcrosses. The incidence and behavior of melanoma in these mice were monitored. A high incidence (80–100%) of spontaneous amelanotic melanoma was observed in albino transgenic mice derived from backcrosses with A, AKR, FVB, and SJL strains. The lowest incidence (30%) was obtained in BALB/c‐derived crosses. No tumors were observed in non‐transgenic mice. Immunohistochemical and western blot analyses using antibodies against three melanocyte‐specific markers of the tyrosinase family of proteins confirmed that the tumors were composed of amelanotic melanocytes. Furthermore, the presence of numerous premelanosomes observed by electron microscopy further supported the melanocytic origin of these tumors. Previous in vitro studies on human melanoma have suggested that cutaneous amelanotic melanoma was evolving from pre‐existing pigmented cutaneous melanoma. However, our results indicate that it can occur directly, as evidenced by the appearance of cutaneous amelanotic melanoma in the tyrosinase‐deficient albino mice. These mice represent a potentially valuable model for studying the mechanistic, diagnostic, and therapeutic features of this highly malignant neoplasm.