c-Myb regulates matrix metalloproteinases 1/9, and cathepsin D: implications for matrix-dependent breast cancer cell invasion and metastasis
Jazyk angličtina Země Velká Británie, Anglie Médium electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
22439866
PubMed Central
PMC3325857
DOI
10.1186/1476-4598-11-15
PII: 1476-4598-11-15
Knihovny.cz E-zdroje
- 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
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.
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