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Matrixmetalloproteinases (MMP), such as type IV collagenases and interstitial collagenases, play an important role in tumor invasion and metastasis. And tissue inhibitor of metalloproteinases (TIMP) inhibit collagenolytic activity of these enzymes. We investigated the gene expressions of MMP-9 (92 kDa type IV collagenase), MMP-2 (72 kDa type IV collagenase), TIMP-1 and TIMP-2 in bladder cancers by Northern blot and slot blot hybridization. The mRNA levels of MMP-2, TIMP-1 and TIMP-2 increased in the cases with invasion and metastasis of bladder cancers. These findings suggest that MMP-2 acts as a regulator of the invasion and metastasis of bladder cancers. The MMP-2/TIMP-2 ratio increased as tumor invasion and metastasis progressed, suggesting that an imbalance in the MMP and TIMP ratio promote the invasion and metastasis of bladder cancers. And we also investigated the gene expressions of c-fos that activate the collagenase genes, and there was a correlation between c-fos and MMP-2 in gene expressions. It is suggested that fos gene may play an important role for the invasion and metastasis in bladder cancers.

GENE EXPRESSIONS OF TYPE IV COLLAGENASE AND TISSUE INHIBITOR OF METALLOPROTEINASES (TIMP) IN HUMAN BLADDER CANCERS