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

k 2017

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

DÚCKA, Monika, Lucia KNOPFOVÁ, Elisabetta BIGLIERI, Markéta HERMANOVÁ, Lubor BORSIG et. al.

Základní údaje

Originální název

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

Autoři

DÚCKA, Monika, Lucia KNOPFOVÁ, Elisabetta BIGLIERI, Markéta HERMANOVÁ, Lubor BORSIG a Petr BENEŠ

Vydání

XVIII. setkání biochemiků a molekulárních biologů, 2017

Další údaje

Typ výsledku

Prezentace na konferencích

Utajení

není předmětem státního či obchodního tajemství

ISBN

978-80-210-8765-1

Změněno: 23. 4. 2019 08:51, Soňa Böhmová

Anotace

V originále

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.

Návaznosti

GJ17-08985Y, projekt VaV

Název: Prozánětlivá signalizace pod kontrolou proteinu c-Myb v bazálních prsních karcinomech

Investor: Grantová agentura ČR, c-Myb-regulated inflammatory circuit in basal-like mammary tumors

Citovat

DÚCKA, Monika, Lucia KNOPFOVÁ, Elisabetta BIGLIERI, Markéta HERMANOVÁ, Lubor BORSIG a Petr BENEŠ. Transcription factor c-Myb suppresses metastasis in human breast cancer xenograft model. In XVIII. setkání biochemiků a molekulárních biologů. 2017. ISBN 978-80-210-8765-1.

@proceedings{1472763,
   author = {Dúcka, Monika and Knopfová, Lucia and Biglieri, Elisabetta and Hermanová, Markéta and Borsig, Lubor and Beneš, Petr},
   booktitle = {XVIII. setkání biochemiků a molekulárních biologů},
   isbn = {978-80-210-8765-1},
   title = {Transcription factor c-Myb suppresses metastasis in human breast cancer xenograft model},
   year = {2017}
}

TY  - CONF
ID  - 1472763
AU  - Dúcka, Monika - Knopfová, Lucia - Biglieri, Elisabetta - Hermanová, Markéta - Borsig, Lubor - Beneš, Petr
PY  - 2017
TI  - Transcription factor c-Myb suppresses metastasis in human breast cancer xenograft model
SN  - 9788021087651
N2  - 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.
ER  -

DÚCKA, Monika, Lucia KNOPFOVÁ, Elisabetta BIGLIERI, Markéta HERMANOVÁ, Lubor BORSIG a Petr BENEŠ. Transcription factor c-Myb suppresses metastasis in human breast cancer xenograft model. In \textit{XVIII. setkání biochemiků a molekulárních biologů}. 2017. ISBN~978-80-210-8765-1.

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