Kato M, Takahashi M, Akhand A A, Liu W, Dai Y, Shimizu S, Iwamoto T, Suzuki H, Nakashima I
Department of Immunology, Nagoya University School of Medicine, Japan.
Oncogene. 1998 Oct 8;17(14):1885-8. doi: 10.1038/sj.onc.1202077.
We report here on a novel metallothionein-I (MT)/ret transgenic mouse line in which skin melanosis, benign melanocytic tumor and malignant melanoma metastasizing to distant organs develop stepwise. The process of tumor development and its malignant transformation in this line may resemble that of the human giant congenital melanocytic nevus that is present at birth and that frequently gives rise to malignant melanoma during aging. We observed an increase in the expression level and activity of the ret transgene during the disease progression. That increase in transgene expression accompanied an activation of mitogen-activated protein kinases (MAPKs) and c-Jun as well as matrix metalloproteinases. These results suggest that progressive dysregulation of the expression level of the ret transgene might play a crucial role in the malignant transformation of melanocytic tumors developed in the MT/ret transgenic mouse line.
我们在此报告一种新型的金属硫蛋白-I（MT）/ret转基因小鼠品系，在该品系中，皮肤黑素沉着、良性黑素细胞肿瘤以及转移至远处器官的恶性黑色素瘤会逐步发展。该品系中肿瘤的发生及其恶性转化过程可能类似于人类出生时即存在的巨大先天性黑素细胞痣，且该痣在衰老过程中经常引发恶性黑色素瘤。我们观察到在疾病进展过程中ret转基因的表达水平和活性增加。转基因表达的增加伴随着丝裂原活化蛋白激酶（MAPK）、c-Jun以及基质金属蛋白酶的激活。这些结果表明，ret转基因表达水平的渐进性失调可能在MT/ret转基因小鼠品系中发生的黑素细胞肿瘤的恶性转化中起关键作用。
