Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines

• Published in: International journal of molecular sciences Vol. 19; no. 7; p. 1918
• Main Authors: Marchwicka, Aleksandra, Marcinkowska, Ewa
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.06.2018; MDPI
• Subjects: Acute myeloid leukemia; Blotting, Western; CCAAT-Enhancer-Binding Protein-beta - genetics; CCAAT-Enhancer-Binding Protein-beta - metabolism; CCAAT-Enhancer-Binding Protein-delta - genetics; CCAAT-Enhancer-Binding Protein-delta - metabolism; CCAAT-enhancer-binding proteins; CCAAT/enhancer-binding protein; CEBP genes; Data points; Differentiation; Flow Cytometry; Gene expression; Gene Silencing; Genes; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - genetics; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - metabolism; HL-60 Cells; Humans; Leukemia; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - metabolism; Myeloid leukemia; nuclear receptors; Proteins; Receptors, Calcitriol - genetics; Receptors, Calcitriol - metabolism; Regulators; Retinoic acid; Retinoic Acid Receptor alpha - genetics; Retinoic Acid Receptor alpha - metabolism; retinoic acid receptor α; Transcription factors; Tretinoin; Tumor cell lines; Vitamin D; vitamin D receptor; Vitamin D receptors; nuclear receptors; differentiation; CCAAT-enhancer-binding proteins; acute myeloid leukemia; retinoic acid receptor α; vitamin D receptor; CEBP genes
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms19071918

All-trans-retinoic acid (ATRA) and 1α,25-dihydroxyvitamin D (1,25D) are potent inducers of differentiation of myeloid leukemia cells. During myeloid differentiation specific transcription factors are expressed at crucial developmental stages. However, precise mechanism controlling the diversification of myeloid progenitors is largely unknown, CCAAT/enhancer-binding protein (C/EBP) transcription factors have been characterized as key regulators of the development and function of the myeloid system. Past data point at functional redundancy among C/EBP family members during myeloid differentiation. In this study, we show that in acute myeloid leukemia (AML) cells, high expression of vitamin D receptor gene ( ) is needed for strong and sustained upregulation of gene, while the moderate expression of is sufficient for upregulation of in response to 1,25D. The high expression level of the gene encoding for retinoic acid receptor α ( ) allows for high and sustained expression of , which becomes decreased along with a decrease of expression. Expression of induced by ATRA is accompanied by upregulated expression of with similar kinetics. Our results suggest that is the major VDR and RARA-responsive gene among the family, necessary for expression of genes connected with myeloid functions.