title: Nuclear factor of activated T-cells 1 increases sensitivity of v-myb transformed monoblasts to all-trans retinoic acid.
abstract: 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.
authors.affiliation: Department of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37 Brno, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Trčka
authors.forename: Jan
authors.initials: J
authors.lastname: Šmarda
authors.forename: Lucia
authors.initials: L
authors.lastname: Knopfová
authors.forename: Kateřina
authors.initials: K
authors.lastname: Kuziaková
authors.forename: Petr
authors.initials: P
authors.lastname: Beneš
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D061207:Calcium Ionophores / Q000494:pharmacology; D020013:Calcium Signaling; D002454:Cell Differentiation; D049109:Cell Proliferation; D002478:Cells, Cultured; D019925:Cyclin A / Q000378:metabolism; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D055017:Monocyte-Macrophage Precursor Cells / Q000502:physiology*; D050778:NFATC Transcription Factors / Q000502:physiology*; D020626:Oncogene Proteins v-myb / Q000502:physiology*; D010587:Phagocytosis; D020239:Receptor Cross-Talk; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D016897:Respiratory Burst; D000072482:Retinoic Acid Receptor alpha; D015533:Transcriptional Activation; D014212:Tretinoin / Q000494:pharmacology* / Q000502:physiology
chemical_list: D061207:Calcium Ionophores; D019925:Cyclin A; D050778:NFATC Transcription Factors; D020626:Oncogene Proteins v-myb; C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D015759:Ionomycin; D014212:Tretinoin