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.

scholarly journals 9-cis-retinoic acid is a natural antagonist for the retinoic acid receptor response pathway

1993 ◽  
Vol 295 (2) ◽  
pp. 343-346 ◽  
Author(s):  
C Carlberg ◽  
J H Saurat ◽  
G Siegenthaler
Keyword(s):  
Retinoic Acid ◽  
Retinoic Acid Receptor ◽  
Retinoic Acid Receptors ◽  
Dependent Manner ◽  
Receptor Response ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
X Receptors ◽  
Dose Dependent

The pleiotropic activities of retinoids are mediated by two types of nuclear receptors, the retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). All-trans-retinoic acid (RA) transcriptionally activates RARs, but not RXRs, whereas its natural stereoisomer, 9-cis-RA, is the ligand for RXRs. Here, we demonstrate that 9-cis-RA did not transcriptionally activate RARs, whereas in the presence of all-trans-RA the transactivation of RARs was inhibited in a dose-dependent manner by 9-cis-RA. RAR homodimer complexes were destabilized in vitro in the presence of 9-cis-RA. This suggests that 9-cis-RA may be a natural antagonist of all-trans-RA for binding to RAR complexes. The levels of 9-cis-RA may determine by which pathway the transcription of retinoid-responsive genes is modulated.

scholarly journals Multiple retinoid-responsive receptors in a single cell: families of retinoid "X" receptors and retinoic acid receptors in the Xenopus egg.

1992 ◽  
Vol 89 (6) ◽  
pp. 2321-2325 ◽  
Author(s):  
B. Blumberg ◽  
D. J. Mangelsdorf ◽  
J. A. Dyck ◽  
D. A. Bittner ◽  
R. M. Evans ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Single Cell ◽  
Retinoic Acid Receptors ◽  
Retinoid X Receptors ◽  
Xenopus Egg ◽  
X Receptors

scholarly journals DNA Methylation Predicts the Response of Triple-Negative Breast Cancers to All-Trans Retinoic Acid

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 397 ◽  
Author(s):  
Krysta Coyle ◽  
Cheryl Dean ◽  
Margaret Thomas ◽  
Dejan Vidovic ◽  
Carman Giacomantonio ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Retinoic Acid ◽  
Cell Lines ◽  
Triple Negative ◽  
Atra Treatment ◽  
Response Elements ◽  
Acid Binding Protein ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid

All-trans retinoic acid (atRA) regulates gene expression and is used to treat acute promyelocytic leukemia. Attempts to use atRA in breast cancer without a stratification strategy have resulted in limited overall effectiveness. To identify biomarkers for the treatment of triple-negative breast cancer (TNBC) with atRA, we characterized the effects of atRA on the tumor growth of 13 TNBC cell lines. This resulted in a range of effects that was not predictable based on previously hypothesized predictors of response, such as the levels of atRA nuclear shuttling proteins fatty acid binding protein 5 (FABP5) and cellular retinoic acid binding protein 2 (CRABP2). Transcriptional profiling revealed that atRA induced distinct gene expression changes in the sensitive versus resistant cell lines that were mostly independent of the presence of retinoic acid response elements (RAREs) or peroxisome proliferator response elements (PPREs). Given the importance of DNA methylation in regulating gene expression, we hypothesized that differential DNA methylation could predict the response of TNBCs to atRA. We identified over 1400 sites that were differentially methylated between atRA resistant and sensitive cell lines. These CpG sites predicted the response of four TNBC patient-derived xenografts to atRA, and we utilized these xenografts to refine the profile and identified that as many as 17% of TNBC patients could benefit from atRA treatment. These data illustrate that differential methylation of specific CpGs may be useful biomarkers for predicting the response of patient tumors to atRA treatment.

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