scholarly journals Critical role of both retinoid nuclear receptors and retinoid-X-receptors in mediating growth inhibition of ovarian cancer cells by all-trans retinoic acid

Oncogene ◽  
1998 ◽  
Vol 17 (22) ◽  
pp. 2839-2849 ◽  
Author(s):  
Shujian Wu ◽  
Dongmei Zhang ◽  
Zhen-Ping Zhang ◽  
Dianne Robert Soprano ◽  
Kenneth J Soprano
Keyword(s):  
Ovarian Cancer ◽  
Retinoic Acid ◽  
Nuclear Receptors ◽  
Critical Role ◽  
Ovarian Cancer Cells ◽  
Retinoid X Receptors ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
X Receptors

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.

scholarly journals All-trans retinoic acid downregulates ALDH1-mediated stemness and inhibits tumour formation in ovarian cancer cells

2015 ◽  
Vol 36 (4) ◽  
pp. 498-507 ◽  
Author(s):  
Ming-Jer Young ◽  
Yi-Hui Wu ◽  
Wen-Tai Chiu ◽  
Tzu-Yu Weng ◽  
Yu-Fang Huang ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Retinoic Acid ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Tumour Formation

scholarly journals Activation of retinoid X receptors induces apoptosis in HL-60 cell lines.

1995 ◽  
Vol 15 (7) ◽  
pp. 3540-3551 ◽  
Author(s):  
L Nagy ◽  
V A Thomázy ◽  
G L Shipley ◽  
L Fésüs ◽  
W Lamph ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Cell Lines ◽  
Cellular Differentiation ◽  
Retinoic Acid Receptors ◽  
Retinoid X Receptors ◽  
Ligand Activation ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Induction Of Apoptosis ◽  
X Receptors

Retinoids induce myeloblastic leukemia (HL-60) cells to differentiate into granulocytes, which subsequently die by apoptosis. Retinoid action is mediated through at least two classes of nuclear receptors: retinoic acid receptors, which bind both all-trans retinoic acid and 9-cis retinoic acid, and retinoid X receptors, which bind only 9-cis retinoic acid. Using receptor-selective synthetic retinoids and HL-60 cell sublines with different retinoid responsiveness, we have investigated the contribution that each class of receptors makes to the processes of cellular differentiation and death. Our results demonstrate that ligand activation of retinoic acid receptors is sufficient to induce differentiation, whereas ligand activation of retinoid X receptors is essential for the induction of apoptosis in HL-60 cell lines.

Developmental role of endogenous retinoids in the determination of morphallactic field in budding tunicates

Development ◽  
1993 ◽  
Vol 117 (3) ◽  
pp. 835-845 ◽  
Author(s):  
K. Kawamura ◽  
K. Hara ◽  
S. Fujiwara
Keyword(s):  
Retinoic Acid ◽  
Aldehyde Dehydrogenase ◽  
Ectopic Expression ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Proximal Extremity ◽  
Developmental Role

We have extracted retinoids from the budding tunicate Polyandrocarpa misakiensis and, using HPLC, identified some major peaks as cis-retinal, all-trans-retinal and all-trans-retinoic acid, of which cis-retinal was most abundant (~2 micromolar). In developing buds, the amount of cis-retinal was about one-fifth that of the adult animals. In those buds, aldehyde dehydrogenase, which could metabolize retinal in vitro, was expressed in epithelial cells and then in mesenchymal cells at the proximal extremity, that is, the future developmental field of the bud. Exogenous retinoic acid comparable to the endogenous level could induce an additional field at the distal end of the bud, resulting in a double monster. The induction always accompanied an ectopic expression of aldehyde dehydrogenase. The results of this work suggest that retinoic acid or related molecule(s) act as an endogenous trigger of morphallactic development of Polyandrocarpa buds.

scholarly journals Retinoic acid modulation of glutathione and cysteine metabolism in chondrocytes

1996 ◽  
Vol 314 (1) ◽  
pp. 21-26 ◽  
Author(s):  
Cristina C. TEIXEIRA ◽  
Irving M. SHAPIRO ◽  
Masashi HATORI ◽  
Ramesh RAJPUROHIT ◽  
Cameron KOCH
Keyword(s):  
Ascorbic Acid ◽  
Superoxide Dismutase ◽  
Retinoic Acid ◽  
Critical Role ◽  
Phosphate Concentration ◽  
Antioxidant Systems ◽  
Chondrocyte Maturation ◽  
Medium Components ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

The major objective of this investigation was to determine the thiol status of chondrocytes and to relate changes in the level of glutathione and cysteine to maturation of the cells as they undergo terminal differentiation. Chondrocytes were isolated from the cephalic portion of chick embryo sterna and treated with all-trans retinoic acid for one week. We found that the addition of 100 nM retinoic acid to the cultures decreased the intracellular levels of glutathione and cysteine from 6.1 to 1.6 and 0.07 to 0.01 nmol/μg DNA respectively; retinoic acid also caused a decrease in the extracellular concentration of cysteine. The decrease in chondrocyte thiols was dose and time dependent. To characterize other antioxidant systems of the sternal cell culture, the activities of catalase, glutathione reductase and superoxide dismutase were determined. Activities of all of those enzymes were high in the retinoic acid-treated cells; the conditioned medium also contained these enzymes and the cytosolic isoenzyme of superoxide dismutase. We probed the specificity of the thiol response by using immature caudal chondrocytes. Unlike the cephalic cells, retinoic acid did not change intracellular glutathione and extracellular cysteine levels, although the retinoid caused a reduction in the intracellular cysteine concentration. Finally, we explored the effect of medium components on chondrocyte thiol status. We noted that while ascorbate alone did not change cell thiol levels, it did cause a 4-fold decrease in the extracellular cysteine concentration. When retinoic acid and ascorbic acid were both present in the medium, there was a marked decrease in the level of glutathione. In contrast, the phosphate concentration of the culture medium served as a powerful modulator of both glutathione and cysteine. Results of the study clearly showed that there is a profound decrease in intracellular levels of both cysteine and glutathione and that thiol levels are responsive to ascorbic acid and the medium phosphate concentration. These findings point to a critical role for thiols in modulating events linked to chondrocyte maturation and cartilage matrix synthesis and mineralization.

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