Enhanced RNA expression of tissue inhibitor of metalloproteinases-1 (TIMP-1) in human breast cancer.

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is known to have at least 2 distinct types of activity, i.e., as a regulator of collagenolytic activity, and erythroid potentiating activity (EPA). In this study, we examined the expression of TIMP-1 in human mammary carcinomas, non-malignant breast tissues and benign breast tumors. A total of 53 samples were subjected to Northern-blot analysis, including 23 of primary breast cancer, 26 of non-malignant breast tissues, and 4 benign tumors. Of the 53 samples, 10 were paired malignant and non-malignant breast-tissue samples from the same patient. TIMP-1 RNA expression was significantly higher in the malignant tumor tissues than in the non-malignant counterpart. Similar differences were observed in the level of TIMP-1 protein expression in the paired breast samples examined. Moreover, breast-cancer cell lines secreted larger amounts of TIMP-1 in vitro than non-neoplastic breast epithelial lines. The up-regulation of TIMP-1 expression in breast cancer may suggest that TIMP-1 has an additional role to that of metalloproteinase inhibitor.