Up-regulated p27^Kip1 Reduces Matrix Metalloproteinase-9 and Inhibits Invasion of Human Breast Cancer Cells

Abstract

Background: p27^Kip1 is a cyclin-dependent kinase inhibitor which has been reported to be associated with invasion, metastasis and angiogenesis in malignant tumors, but its mechanism of action remains unknown. Here, it was examined whether p27^Kip1 has an inhibitory effect on cancer cell invasion and correlates with matrix metalloproteinase expression (MMPs). Material and methods: The human breast cancer cell line MDA-MB-231 and MDA-MB-231 transfected p27^Kip1 MDA-MB-p27 were used for the invasion assay, Western blotting and real-time quantitative RT-PCR. Results: In the invasion assay, the invasion of MDA-MB-p27 was significantly less than that of the parent cell line. In Western blotting analyses, the protein level of MMP-9 was also reduced in MDA-MB-p27. Furthermore, the activity of MMP-9 in cell culture supernatants was lower in MDA-MB-p27 as compared with enzyme-linked immunosorbent assays. In real-time quantitative RT-PCR, the mRNA level of MMP-9 was lower in MDA-MB-p27 cells. Conclusion: Up-regulation of p27^Kip1 remarkably inhibited the invasion of the breast cancer cells, in part due to the reduced expression of MMP-9. This is the first report of p27^Kip1 modulating MMP-9 and indicating that p27^Kip1 might play a key role in tumor cell invasion.