Nuclear factor of activated T-cells 1 increases sensitivity of v-myb transformed monoblasts to all-trans retinoic acid

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Authors

TRČKA Filip ŠMARDA Jan KNOPFOVÁ Lucia KUZIAKOVÁ Kateřina BENEŠ Petr

Year of publication 2013
Type Article in Periodical
Magazine / Source Cellular Signalling
MU Faculty or unit

Faculty of Science

Citation
Doi http://dx.doi.org/10.1016/j.cellsig.2013.03.021
Field Genetics and molecular biology
Keywords Differentiation; Myeloid cells; NFAT1; Proliferation; Retinoic acid; v-Myb
Description Nuclear factors of activated T-cells (NFATs) are important regulators of the cytokine gene expression in activated T-cells. In the last decade, NFATs have been shown to regulate cell cycle, differentiation and apoptosis in cells of various origins revealing their importance for cell homeostasis. In this study, we investigated the effects of NFAT1 on proliferation and differentiation of v-myb-transformed BM2 monoblasts. In contrast to many other leukemic cell lines, BM2 cells do not respond to retinoic acid. However, once overexpressing NFAT1, they became sensitive to all-trans retinoic acid (ATRA). The ATRA-treated BM2NFAT1 cells differentiated along monocyte/macrophage pathway as evidenced by changes in cell morphology, adherence, phagocytic and non-specific esterase activities, reactive oxygen species production, and vimentin expression. Furthermore, overexpressed NFAT1 either alone or in combination with the ATRA-driven signalling pathway deregulated cyclin A and retinoic acid receptor proteins in BM2 cells. Data presented in this study indicate that the NFAT1 and ATRA signalling pathways synergize in control of proliferation and differentiation of BM2 monoblasts.
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