Proliferation and neoplastic transformation of pigment cells in metallothionein/ret transgenic mice.
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.
Takahashi
M
M
Department of Pathology, Nagoya University School of Medicine, Japan.
Iwamoto
T
T
Nakashima
I
I
D000818:Animals; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000473:pathology*; D029721:Drosophila Proteins; D015870:Gene Expression; D008544:Melanocytes / Q000166:cytology*; D008668:Metallothionein / Q000235:genetics* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000502:physiology; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases
D029721:Drosophila Proteins; D011518:Proto-Oncogene Proteins; D008668:Metallothionein; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C494999:Ret protein, mouse