TRANSGENIC MOUSE MODEL FOR SKIN MALIGNANT-MELANOMA

We report here on a novel metallothionein-I (MT)/ret transgenic mouse line in which skin melanosis, benign melanocytic tumor and malignant m elanoma 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 act ivity of the ret transgene during the disease progression. That increa se in transgene expression accompanied an activation of mitogen-activa ted protein kinases (MAPKs) and c-Jun as well as matrix metalloprotein ases. These results suggest that progressive dysregulation of the expr ession level of the ret transgene might play a crucial role in the mal ignant transformation of melanocytic tumors developed in the MT/ret tr ansgenic mouse line.