scholarly journals Transcriptomic analysis of all-trans retinoic acid (ATRA)-, 16keto-estradiol (16KE2)- and 1,25-dihydroxyvitamin D3 (125DVD3)-treated HL-60 cells

2015 ◽  
Author(s):  
K Stegmaier
Keyword(s):  
Retinoic Acid ◽  
Transcriptomic Analysis ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

scholarly journals Role of nitric oxide in the anti-tumoral effect of retinoic acid and 1,25-dihydroxyvitamin D3 on human promonocytic leukemic cells

Blood ◽  
1996 ◽  
Vol 88 (9) ◽  
pp. 3528-3534 ◽  
Author(s):  
N Dugas ◽  
MD Mossalayi ◽  
A Calenda ◽  
A Leotard ◽  
P Becherel ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Retinoic Acid ◽  
Cell Differentiation ◽  
U937 Cell ◽  
Leukemic Cells ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All trans retinoic acid and vitamin D3 derivatives are well known for their antileukemic activity, while the precise mechanism of this effect remains to be clarified. Using human leukemic U937 and THP-1 promonocytic cell lines, we analyzed the effect of all-trans retinoic acid (RA) and/or 1,25-dihydroxyvitamin D3 (VD) on the generation of nitric oxide (NO), a potent antitumoral mediator. U937 cell differentiation with VD or with both RA and VD (RA/VD) correlated with gene transcription and functional expression of inducible nitric oxide synthase (iNOS). Nitrites and L-citrulline were also detected in U937 cell supernatants as soon as 24 hours following cell incubation with VD or RA/VD, but not in cells treated with RA alone. Inhibition of iNOS activity by NG-monomethyl-L-arginine (LNMMA) significantly decreased in vitro U937 cell differentiation with VD and RA/VD as shown by the expression of cell differentiation markers (CD14 and CD68) and by the capacity of these cells to undergo a luminol-dependent chemiluminescence in response to opsonized zymosan. Similar results were obtained using the THP-1 cell line strengthening the role of NO in the VD- and RA/VD-induced growth arrest and terminal differentiation of promonocytic leukemia cells.

The Role of Transcriptional Coactivator TRAP220/MED1 in Nuclear Receptor-Mediated Myelomonocytic Differentiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2727-2727
Author(s):  
Mitsuhiro Ito ◽  
Norinaga Urahama ◽  
Akiko Sada ◽  
Kimikazu Yakushijin ◽  
Katsuya Yamamoto ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Nuclear Receptor ◽  
Precursor Cells ◽  
Mediator Complex ◽  
Dihydroxyvitamin D3 ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Hematopoietic Precursor

Abstract The TRAP/Mediator complex, the metazoan counterpart of the yeast Mediator complex, is master transcriptional regulatory complex composed of approximately 30 subunits. It was originally isolated as a thyroid hormone receptor (TR)-associated protein (TRAP) complex that mediates TR-activated transcription from DNA templates in vitro and probably acts in vivo after the action of other receptor-interacting coactivators involved in chromatin remodeling. The TRAP220/MED1 subunit of the TRAP/Mediator complex is proposed to act on a variety of major and specific biological events, including growth, differentiation and homeostasis, through physical interaction with nuclear receptors. The vitamin D receptor (VDR) and retinoic acid receptor (RAR), coupled with retinoid X receptor (RXR), are nuclear receptors which have important roles for monopoiesis and granulopoiesis, respectively. In this study, we present the functional role of TRAP220/MED1 in nuclear receptor-mediated monopoiesis and granulopoiesis. Since TRAP220 knockout (Trap220-/-) mice were mortalities during the early embryonic period before definitive hematopoiesis within the hepatic primordia becomes dominant, the function of TRAP220/MED1 in adult hematopoiesis was mostly unknown. However, these embryos appeared to have normal composition of nucleated erythroid cells. Therefore, the E9.0 yolk sac-derived hematopoietic precursor cells were used to differentiate into definitive hematopoietic colony forming units within the methylcellulose blood cell culture. The number of monocytic colonies (CFU-M) was significantly lower in knockouts than in wild type controls, while the numbers of other types of colonies (CFU-GEMM, CFU-GM, CFU-G and CFU-E) were comparable. Hence, TRAP220/MED1 appeared to be indispensable for optimal monocytic differentiation. Next, the HL-60 acute promyelocytic leukemia cells were used to elucidate directly and mechanistically the roles of TRAP220/MED1 in RAR- and VDR-dependent differentiation of the hematopoietic precursor cells into granulocytic and monocytic lineage cells. The expression of the TRAP220/MED1 subunit as well as other TRAP/Mediator subunits was induced when the cells were treated with their ligands, all-trans retinoic acid and 1,25-dihydroxyvitamin D3. Flow cytometric analyses showed that HL-60 cells, wherein TRAP220/MED1 was down-regulated, did not differentiate efficiently into monocytes and granulocytes by stimulation with 1,25-dihydroxyvitamin D3 and all-trans retinoic acid, correspondingly. The expression of direct target genes of VDR or RAR, as well as the differentiation marker genes, was low in the knockdown cells by stimulation with these ligands. In contrast, 12-O-tetradecanoylphorbol-13-acetate (TPA)- and dimethylsulphoxide (DMSO)-mediated monocytic and myeloid differentiation, which bypasses nuclear receptor-mediated signaling pathways, was not affected in knockdown cells. Collectively, these results indicated an indispensable role of TRAP220/MED1 in the optimal VDR- and RAR-mediated myelomonocytic differentiation processes in mammalian hematopoiesis.

Cooperative Action of 1alpha,25-Dihydroxyvitamin D3 and Retinoic Acid in NB4 Acute Promyelocytic Leukemia Cell Differentiation Is Transcriptionally Controlled.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4247-4247
Author(s):  
Jean-Noel Bastie ◽  
Nicole Balitrand ◽  
Isabelle Guillemot ◽  
Christine Chomienne ◽  
Laurent Delva
Keyword(s):  
Retinoic Acid ◽  
Transcriptional Activity ◽  
Target Genes ◽  
Leukemia Cell ◽  
Leukemic Cells ◽  
Dihydroxyvitamin D3 ◽  
Nb4 Cells ◽  
Cooperative Action ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

Abstract All-trans-retinoic acid (RA) and 1alpha,25-dihydroxyvitamin D3 (1,25D3) are involved in the control of hematopoiesis and have been suggested to play a role in cellular differentiation and are as such potent inducers of differentiation of myeloid leukemia cells. In this study, we have shown that in promyelocytic NB4 cells, addition of 1,25D3 enhances terminal granulocytic RA-dependent differentiation concomitant with the enhanced activation of the RA-transcriptional activity through an RARbeta promoter. By EMSA and ChIP assays, we further demonstrate that while both VDR and RAR are bound to the RARbeta promoter in NB4 cells, addition of 1,25D3 increases VDR binding to this promoter while that of RA induces the release of VDR and increases the binding of RAR. Thus, contrary to normal myeloid cells, 1,25D3 does not act as a transrepressor of RA-transcriptional activity in leukemic cells suggesting that transcriptional regulation of RA-target genes may be modified in malignant cells. In promyelocytic leukemic cells the combination of 1,25D3 and RA results in both enhanced transactivation and differentiation.

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