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.

• MeSH
• Electrophoresis, Polyacrylamide Gel MeSH
• Immunoblotting MeSH
• Cathepsin D genetics   metabolism   MeSH
• Real-Time Polymerase Chain Reaction MeSH
• Humans MeSH
• RNA, Small Interfering MeSH
• Matrix Metalloproteinase 1 genetics   metabolism   MeSH
• Matrix Metalloproteinase 9 genetics   metabolism   MeSH
• Neoplasm Metastasis genetics   physiopathology   MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Cell Line, Tumor MeSH
• Breast Neoplasms genetics   metabolism   MeSH
• Cell Movement genetics   physiology   MeSH
• Proto-Oncogene Proteins c-myb genetics   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cathepsin D MeSH
• RNA, Small Interfering MeSH
• Matrix Metalloproteinase 1 MeSH
• Matrix Metalloproteinase 9 MeSH
• Proto-Oncogene Proteins c-myb MeSH