title: c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis.
abstract: BACKGROUND
  The c-Myb transcription factor is essential for the maintenance of stem-progenitor cells in bone marrow, colon epithelia, and neurogenic niches. c-Myb malfunction contributes to several types of malignancies including breast cancer. However, the function of c-Myb in the metastatic spread of breast tumors remains unexplored. In this study, we report a novel role of c-Myb in the control of specific proteases that regulate the matrix-dependent invasion of breast cancer cells.
  
  
  RESULTS
  Ectopically expressed c-Myb enhanced migration and ability of human MDA-MB-231 and mouse 4T1 mammary cancer cells to invade Matrigel but not the collagen I matrix in vitro. c-Myb strongly increased the expression/activity of cathepsin D and matrix metalloproteinase (MMP) 9 and significantly downregulated MMP1. The gene coding for cathepsin D was suggested as the c-Myb-responsive gene and downstream effector of the migration-promoting function of c-Myb. Finally, we demonstrated that c-Myb delayed the growth of mammary tumors in BALB/c mice and affected the metastatic potential of breast cancer cells in an organ-specific manner.
  
  
  CONCLUSIONS
  This study identified c-Myb as a matrix-dependent regulator of invasive behavior of breast cancer cells.
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, and International Clinical Research Center, CBCE, St. Anne's University Hospital, Brno, Czech Republic.
authors.forename: Lucia
authors.initials: L
authors.lastname: Knopfová
authors.forename: Petr
authors.initials: P
authors.lastname: Beneš
authors.forename: Lucie
authors.initials: L
authors.lastname: Pekarčíková
authors.forename: Markéta
authors.initials: M
authors.lastname: Hermanová
authors.forename: Michal
authors.initials: M
authors.lastname: Masařík
authors.forename: Zuzana
authors.initials: Z
authors.lastname: Pernicová
authors.forename: Karel
authors.initials: K
authors.lastname: Souček
authors.forename: Jan
authors.initials: J
authors.lastname: Smarda
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D015151:Immunoblotting; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis / Q000235:genetics / Q000503:physiopathology; D020598:Proto-Oncogene Proteins c-myb / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D020598:Proto-Oncogene Proteins c-myb; D034741:RNA, Small Interfering; D002402:Cathepsin D; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1