Breast Cancer Metastasis and the Balance of the Serine Protease Matriptase and Its Inhibitor KSPI-1.

摘要

This study set out to evaluate the biological consequences of a shift in the ratio of the serine protease matriptase relative to its cognate inhibitor HAI-1. The goal of this work is to generate data that we believe will assist in evaluating whether the matriptase HAI-1 system plays a role in breast cancer invasion and metastasis. In order to alter protease/inhibitor ratios we proposed to use a tetracycline regulable expression system to either increase matriptase levels by overexpression or reduce HAI-1 levels by expression of a ribozyme targeted to the HAI-1 mRNA. Although we have encountered significant technical difficulties with this project, we have made considerable progress. Having obtained a full length cDNA clone of matriptase we generated cell lines that over express the gene in an inducible fashion and have started to evaluate the biological consequences of such overexpression. Thus far we have found that such overexpression has no effect on cell proliferation or on the synthesis or activation of two matrix metallo proteases - MMP-2 and MMP-9. Work is rapidly proceeding on the remaining studies.