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Funkce proteinu c-Myb ve vybraných aspektech kancerogeneze

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Title in English Function of the c-Myb protein in selected aspects of cancerogenesis


Year of publication 2013
Type Article in Periodical
Magazine / Source Informační listy
MU Faculty or unit

Faculty of Science

Field Genetics and molecular biology
Keywords c-Myb, breast cancer, migration, invasion, metastasis, extravasation, matrix metalloproteinase, cathepsin D, extracellular matrix
Description 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. The aim of this study is to clarify the role of c-Myb in invasion and metastatic spread of breast tumor cells. We demonstrated that MYB overexpression affected cell migration and invasion in vitro in a context-dependent manner, depending on the presence of chemoatractant or composition of matrix. Surprisingly, the growth of tumors resulting from injection of Myb-overexpressing 4T1 cells into the mammary fat pads of BALB/c mice was delayed and formation of spontaneous pulmonary metastases did not occur, though formation of the bone and liver metastases was not affected. The selective disadvantage of these cells in lung colonization might result from their inability to penetrate a vessel wall and underlying basement membrane in lung parenchyma. We demonstrated that capacity of transendothelial migration of MDA-MB-231MYBup cells was impaired. We identified several genes with deregulated expression in MYBup cells, including CTSD, MMP1 and MMP9. The proteins coded by these genes (cathepsin D, matrix metalloproteinase 1 and 9) together with components of JNK (c-Jun NH2-terminal kinase) signaling pathway may represent the key determinants of the Myb-induced effects on cell migration and invasion in vitro. On the other hand, the Myb-driven suppression of Mmp1a and Msn expression in 4T1 cells may explain the failure of the Myb-overexpressing tumors in lung colonization. The expression profiles of human breast carcinoma specimens deposited in Oncomine and GEO databases indicate that the Myb-mediated repression of MMP1/MSN might be of clinical relevance for breast carcinoma patients.
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