Takahashi M, Iwamoto T, Nakashima I
Department of Pathology, Nagoya University School of Medicine, Japan.
Pigment Cell Res. 1992 Nov;5(5 Pt 2):344-7. doi: 10.1111/j.1600-0749.1992.tb00560.x.
Although melanoma is a common human disease, there were few animal models in which melanoma developed at high incidence. To date, the Xiphophorus fish has been used as a model system to study melanoma formation. Studies on this fish showed the presence of a dominant oncogene, Tu, which encodes a transmembrane, tyrosine kinase of epidermal growth factor receptor type (Wittbrodt et al., Nature, 341:415-421, 1989). Recently, we succeeded in establishing novel transgenic mouse lines in which melanosis and melanocytic tumors developed stepwise by introducing another transmembrane tyrosine kinase oncogene, ret (Iwamoto et al., EMBO J., 10:3167-3175, 1991). In our transgenic mice, high levels of expression of the ret transgene induced proliferation and neoplastic transformation of melanin-producing cells. In addition, crossbreeding experiments between transgenic mice and Wv mice showed that the ret oncogene can also induce melanogenesis and melanocyte development in Wv/Wv mice.
尽管黑色素瘤是一种常见的人类疾病，但很少有动物模型能高发病率地发生黑色素瘤。迄今为止，剑尾鱼已被用作研究黑色素瘤形成的模型系统。对这种鱼的研究表明存在一种显性致癌基因Tu，它编码一种表皮生长因子受体类型的跨膜酪氨酸激酶（Wittbrodt等人，《自然》，341:415 - 421，1989）。最近，我们成功建立了新型转基因小鼠品系，通过导入另一种跨膜酪氨酸激酶致癌基因ret，黑色素沉着和黑素细胞肿瘤逐步发展（Iwamoto等人，《欧洲分子生物学组织杂志》，10:3167 - 3175，1991）。在我们的转基因小鼠中，ret转基因的高表达诱导了产生黑色素细胞的增殖和肿瘤转化。此外，转基因小鼠与Wv小鼠之间的杂交实验表明，ret致癌基因也能在Wv/Wv小鼠中诱导黑色素生成和黑素细胞发育。
