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
• elektroforéza v polyakrylamidovém gelu MeSH
• imunoblotting MeSH
• kathepsin D genetika   metabolismus   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé MeSH
• malá interferující RNA MeSH
• matrixová metaloproteinasa 1 genetika   metabolismus   MeSH
• matrixová metaloproteinasa 9 genetika   metabolismus   MeSH
• metastázy nádorů genetika   patofyziologie   MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádory prsu genetika   metabolismus   MeSH
• pohyb buněk genetika   fyziologie   MeSH
• protoonkogenní proteiny c-myb genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• kathepsin D MeSH
• malá interferující RNA MeSH
• matrixová metaloproteinasa 1 MeSH
• matrixová metaloproteinasa 9 MeSH
• protoonkogenní proteiny c-myb MeSH