Abstract
PURPOSE: To evaluate the role of RUNX3 in breast cancer pathogenesis, we examined the RUNX3 expression in breast cancer tissues and analyzed the correlation between RUNX3 expression and clinicopathologic variables and patients survival. METHODS: We evaluated the RUNX3 expression by immunohistochemistry using a tissue microarray containing 256 specimens of breast cancer patients. We also studied the role of RUNX3 in cell migration and invasion by performing cell migration and invasion assay. Differential expression of metastasis-related genes after RUNX3 restoration was analyzed using the Human Tumor Metastasis PCR Array. RESULTS: The RUNX3 expression was significantly correlated with breast cancer histology grade (P = 0.000), and low RUNX3 expression strongly correlated with worse 5-year overall and disease-specific survival rates (P = 0.000 and P = 0.001, respectively). Furthermore, we found that RUNX3 restoration suppressed breast cancer metastasis by controlling cell migration and invasion capacity. Finally, gene expression profiles of RUNX3-549 and Ctrl-549 cells showed matrix metalloproteinase-2 (MMP-2) was the most significant gene among the 84 metastasis-related genes influenced by RUNX3 reintroduction. CONCLUSIONS: Reduced RUNX3 expression is significantly correlated with breast cancer progression and predicts worse survival. RUNX3 regulates breast cancer cell migration and invasion through the MMP-2 pathway.