Differential regulation of MMP-9 and TIMP-2 expression in malignant melanoma developed in Metallothionein/RET transgenic mice

We recently established a metallothionein-I(MT)/RET transgenic mouse line i n which skin melanosis, benign melanocytic tumor and malignant melanoma dev elop stepwise. Malignant melanoma cells but not benign melanocytic tumor ce lls had metastatic ability in transgenic mice. In the present study, we inv estigated the expression of several matrix metalloproteinases (MMPs) and ti ssue inhibitors of matrix metalloproteinases (TIMPs), including MMP-1, MMP- 2, MMP-3, MMP-7, MMP-9, MTI-MMP,TIMP-1 and TIMP-2, in these tumors. Western and northern blot analyses revealed that malignant transformation of melan ocytic tumors developed in MT/RET transgenic mice accompanied with upregula tion of MMP-9 and downregulation of TIMP-2. Expression of other MMP and TIM P genes examined was very low or undetectable in both benign and malignant tumors, Since activation of MMP-9 in malignant tumors was detected by gelat in zymography, these results suggest that imbalance of expression of the MM P-9 and TIMP-2 genes might be associated Kith metastatic ability of melanom a cells developed in MT/RET transgenic mice.