title: RUNX3 is a prognostic marker and potential therapeutic target in human breast cancer.
abstract: OBJECTIVE
  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.
authors.affiliation: Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, 84 West Huaihai Road, Xuzhou, 221002, Jiangsu, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Bai
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Yong
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Chen
authors.forename: Wen-Bo
authors.initials: WB
authors.lastname: Song
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Jun-Nian
authors.initials: JN
authors.lastname: Zheng
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D001943:Breast Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000378:metabolism; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D060787:Neoplasm Grading; D011379:Prognosis; D046888:Tissue Array Analysis
chemical_list: D014408:Biomarkers, Tumor; D050677:Core Binding Factor Alpha 3 Subunit; C493729:Runx3 protein, human; D020778:Matrix Metalloproteinase 2