Transcription factor c-Myb suppresses metastasis in human breast cancer xenograft model

Název česky Transkripční faktor c-Myb suprimuje metastázování v xenograftovém modelu lidského prsního karcinomu


Rok publikování 2017
Druh Další prezentace na konferencích
Popis The c-Myb protein encoded by MYB/Myb gene is an essential transcriptional regulator of stem and progenitor cells in bone marrow, colon epithelia, and neurogenic niches in an adult brain. The Myb-targeted genes are involved in control of cell proliferation, differentiation and apoptosis. Deregulated expression of c-Myb has been associated with leukemia and some epithelial cancers, particularly breast and colon cancers. The presence of c-Myb is considered to be essential for the proliferation of ER-positive breast cancer (BC) cells and also a prerequisite for mammary carcinogenesis in murine models. However, according to clinical data, high c-Myb levels are associated with good prognosis for BC patients. Our previous results showed that overexpression of Myb in murine mammary cancer cells 4T1 inhibited the formation of lung metastasis, but did not alter liver and bone metastasis. Using complementary strategies of c-Myb overexpression and in vivo selection of lung metastatic cells we evaluated transcriptional program regulated by c-Myb in 4T1 cells and identified an inflammatory signature required for pulmonary BC metastasis. In present study we used human BC cell line MDA-MB-231 to generate cell lines with ectopic MYB expression (MYBhigh) and CRISPR/Cas9-mediated knock-out of MYB gene (MYB KO). Exploring MYB function in xenograft spontaneous metastatic model we found that overexpression of MYB in MDA-MB-231 reduced not only the number of metastasis in lungs, but also the amount of metastasis in liver and bones. On contrary, MYB deletion resulted in increased metastasis in all three tissues. Mechanism discriminating the organ-specific and general metastasis suppression in the two models remains to be determined.
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