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Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines
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 diversificatio...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073189/ https://www.ncbi.nlm.nih.gov/pubmed/29966306 http://dx.doi.org/10.3390/ijms19071918 |
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author | Marchwicka, Aleksandra Marcinkowska, Ewa |
author_facet | Marchwicka, Aleksandra Marcinkowska, Ewa |
author_sort | Marchwicka, Aleksandra |
collection | PubMed |
description | 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 (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. The high expression level of the gene encoding for retinoic acid receptor α (RARA) allows for high and sustained expression of CEBPB, which becomes decreased along with a decrease of RARA expression. Expression of CEBPB induced by ATRA is accompanied by upregulated expression of CEBPE with similar kinetics. Our results suggest that CEBPB is the major VDR and RARA-responsive gene among the CEBP family, necessary for expression of genes connected with myeloid functions. |
format | Online Article Text |
id | pubmed-6073189 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-60731892018-08-13 Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines Marchwicka, Aleksandra Marcinkowska, Ewa Int J Mol Sci Article 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 (VDR) is needed for strong and sustained upregulation of CEBPB gene, while the moderate expression of VDR is sufficient for upregulation of CEBPD in response to 1,25D. The high expression level of the gene encoding for retinoic acid receptor α (RARA) allows for high and sustained expression of CEBPB, which becomes decreased along with a decrease of RARA expression. Expression of CEBPB induced by ATRA is accompanied by upregulated expression of CEBPE with similar kinetics. Our results suggest that CEBPB is the major VDR and RARA-responsive gene among the CEBP family, necessary for expression of genes connected with myeloid functions. MDPI 2018-06-29 /pmc/articles/PMC6073189/ /pubmed/29966306 http://dx.doi.org/10.3390/ijms19071918 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Marchwicka, Aleksandra Marcinkowska, Ewa Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines |
title | Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines |
title_full | Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines |
title_fullStr | Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines |
title_full_unstemmed | Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines |
title_short | Regulation of Expression of CEBP Genes by Variably Expressed Vitamin D Receptor and Retinoic Acid Receptor α in Human Acute Myeloid Leukemia Cell Lines |
title_sort | regulation of expression of cebp genes by variably expressed vitamin d receptor and retinoic acid receptor α in human acute myeloid leukemia cell lines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073189/ https://www.ncbi.nlm.nih.gov/pubmed/29966306 http://dx.doi.org/10.3390/ijms19071918 |
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