Konference: 2010 6. sympózium a workshop molekulární patologie a histo-cyto-chemie
Kategorie: Nádorová biologie/imunologie/genetika a buněčná terapie
Téma: Workshop on Molecular Pathology
Číslo abstraktu: w002
Autoři: Mgr. Lucia Knopfová, Ph.D.; Mgr. Filip Trčka, Ph.D.; MUDr. Petr Beneš; Prof. RNDr. Jan Šmarda, CSc.
The c-Myb gene codes for transcription factor
that is essential for regulation of hematopoiesis in vertebrates.
Deregulated expression and/or mutation of c-Myb can result in
leukemias. In addition to hematopoietic malignancies, the role of
c-Myb in development of solid tumors has been documented as well.
c-Myb was shown to promote proliferation and inhibit
differentiation/apoptosis of various cancer cells. While the role
of c-Myb in control of these processes has been extensively
studied, there are only a few indications that c-Myb can be
involved in cancer cell invasion and metastatic spread. The aim of
this study was to assess the role of the c-Myb protein in control
of invasion of breast cancer cells.
MDA-MB-231 breast cancer cells were transfected with the c-Myb coding cDNA to prepare MDA-MB-231 MYBup derivatives. The effects of c-Myb overexpression on migration and invasion capacity of these cells were assessed using Cultrex Cell invasion assay (RnD Systems). MDA-MB-231 MYBup cells were significantly more active in both motility and invasion than controls as determined by this assay. In order to reveal dynamics of these processes, we performed real-time analysis of cell migration and invasion using the xCELLigence RT-CA system (Roche). This system is based on non-invasive impedance-based monitoring of the transition of cells through the microporous membrane in real time. This real-time analysis of cell migration/invasion clearly confirmed increased invasive capacity of MDA-MB-231MYBup cells compared to controls. To address the mechanism of c-Myb-enhanced breast cancer cell invasion, we examined the role of c-Myb in control of expression and activity of some of the proteases involved in degradation of extracellular matrix. We found that c-Myb increased production of cathepsin D and matrix metalloproteinases in MDA-MB-231 MYBup cells.
The results of this study showed that c-Myb promotes motility and invasive capacity of breast cancer MDA-MB-231 cells and this effect at least partially results from deregulation of expression/ activity of cathepsin D and some matrix metalloproteinases. These results suggest a novel role of c-Myb protein in control of tumor invasion and metastatic progression.
This work was supported by grants 301/09/1115 of GACR, IAA501630801 of GAAV CR, MUNI/C/0099/2009 of
MDA-MB-231 breast cancer cells were transfected with the c-Myb coding cDNA to prepare MDA-MB-231 MYBup derivatives. The effects of c-Myb overexpression on migration and invasion capacity of these cells were assessed using Cultrex Cell invasion assay (RnD Systems). MDA-MB-231 MYBup cells were significantly more active in both motility and invasion than controls as determined by this assay. In order to reveal dynamics of these processes, we performed real-time analysis of cell migration and invasion using the xCELLigence RT-CA system (Roche). This system is based on non-invasive impedance-based monitoring of the transition of cells through the microporous membrane in real time. This real-time analysis of cell migration/invasion clearly confirmed increased invasive capacity of MDA-MB-231MYBup cells compared to controls. To address the mechanism of c-Myb-enhanced breast cancer cell invasion, we examined the role of c-Myb in control of expression and activity of some of the proteases involved in degradation of extracellular matrix. We found that c-Myb increased production of cathepsin D and matrix metalloproteinases in MDA-MB-231 MYBup cells.
The results of this study showed that c-Myb promotes motility and invasive capacity of breast cancer MDA-MB-231 cells and this effect at least partially results from deregulation of expression/ activity of cathepsin D and some matrix metalloproteinases. These results suggest a novel role of c-Myb protein in control of tumor invasion and metastatic progression.
This work was supported by grants 301/09/1115 of GACR, IAA501630801 of GAAV CR, MUNI/C/0099/2009 of
Datum přednesení příspěvku: 24. 4. 2010
