Regulation of vitamin D receptor expression by retinoic acid receptor alpha in acute myeloid leukemia cells

被引:23
|
作者
Marchwicka, Aleksandra [1 ]
Cebrat, Malgorzata [2 ]
Laszkiewicz, Agnieszka [2 ]
Sniezewski, Lukasz [2 ]
Brown, Geoffrey [3 ]
Marcinkowska, Ewa [1 ]
机构
[1] Univ Wroclaw, Fac Biotechnol, Lab Prot Biochem, Joliot Curie 14a, PL-50383 Wroclaw, Poland
[2] Polish Acad Sci, Inst Immunol & Expt Therapy, Dept Tumor Immunol, Lab Mol & Cellular Immunol, Weigla 12, PL-53114 Wroclaw, Poland
[3] Univ Birmingham, Coll Med & Dent Sci, Sch Immun & Infect, Edgbaston B15 2TT, W Midlands, England
来源
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 2016年 / 159卷
关键词
Vitamin D receptor; Retinoic acid receptor alpha; Expression; mRNA; Target gene; Differentiation; N-TERMINAL VARIANT; DIFFERENTIATION THERAPY; GENE; IDENTIFICATION; GAMMA; ELEMENTS; ANALOGS; ABSENCE;
D O I
10.1016/j.jsbmb.2016.03.013
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 D-3 (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 a (RAR alpha) is responsible for regulating VDR transcription in AML cells. We have shown that a VDR transcriptional variant, originating in exon 1a, is regulated by RARa agonists in AML cells. Moreover, in cells with a high basal level of RARa protein, the VDR gene is transcriptionally repressed as long as RARa agonist is absent. In these cells down-regulation of the level of RARa 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. (C) 2016 The Authors. Published by Elsevier Ltd.
引用
收藏
页码:121 / 130
页数:10
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