Regulation of vitamin D receptor expression by retinoic acid receptor alpha in acute myeloid leukemia cells
| Autor: | Łukasz Śnieżewski, Agnieszka Łaszkiewicz, Malgorzata Cebrat, Ewa Marcinkowska, Geoffrey Brown, Aleksandra Marchwicka |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Myeloid Receptors Retinoic Acid Endocrinology Diabetes and Metabolism mRNA Clinical Biochemistry Gene Expression Expression HL-60 Cells Tretinoin Biology Biochemistry Calcitriol receptor 03 medical and health sciences Endocrinology Calcitriol Differentiation therapy hemic and lymphatic diseases Transcriptional regulation medicine Humans Target gene Vitamin D3 24-Hydroxylase Molecular Biology neoplasms Acute leukemia Gene Expression Regulation Leukemic Retinoic Acid Receptor alpha Myeloid leukemia Cell Biology Retinoic acid receptor Leukemia Myeloid Acute 030104 developmental biology medicine.anatomical_structure Retinoic acid receptor alpha Vitamin D receptor Differentiation Enzyme Induction Cancer research Molecular Medicine Receptors Calcitriol |
| Zdroj: | The Journal of steroid biochemistry and molecular biology. 159 |
| ISSN: | 1879-1220 |
| Popis: | Acute myeloid leukemia (AML) is the predominant acute leukemia among adults, characterized by an accumulation of malignant immature myeloid precursors. A very promising way to treat AML is differentiation therapy using either all-trans-retinoic acid (ATRA) or 1,25-dihydroxyvitamin D3 (1,25D), or the use of both these differentiation-inducing agents. However, the effect of combination treatment varies in different AML cell lines, and this is due to ATRA either down- or up-regulating transcription of vitamin D receptor (VDR) in the cells examined. The mechanism of transcriptional regulation of VDR in response to ATRA has not been fully elucidated. Here, we show that the retinoic acid receptor α (RARα) is responsible for regulating VDR transcription in AML cells. We have shown that a VDR transcriptional variant, originating in exon 1a, is regulated by RARα agonists in AML cells. Moreover, in cells with a high basal level of RARα protein, the VDR gene is transcriptionally repressed as long as RARα agonist is absent. In these cells down-regulation of the level of RARα leads to increased expression of VDR. We consider that our findings provide a mechanistic background to explain the different outcomes from treating AML cell lines with a combination of ATRA and 1,25D. |
| Databáze: | OpenAIRE |
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