scholarly journals Differential Modulation of Androgen Receptor Action by Deoxyribonucleic Acid Response Elements

2003 ◽  
Vol 17 (9) ◽  
pp. 1738-1750 ◽  
Author(s):  
Christoph Geserick ◽  
Hellmuth-Alexander Meyer ◽  
Karina Barbulescu ◽  
Bernard Haendler
Keyword(s):  
Androgen Receptor ◽  
Deoxyribonucleic Acid ◽  
Differential Modulation ◽  
Response Elements ◽  
Receptor Action

scholarly journals Differential modulation of androgen receptor transcriptional activity by the nuclear receptor co-repressor (N-CoR)

2004 ◽  
Vol 379 (3) ◽  
pp. 731-738 ◽  
Author(s):  
Cor A. BERREVOETS ◽  
Arzu UMAR ◽  
Jan TRAPMAN ◽  
Albert O. BRINKMANN
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Conformational Change ◽  
Nuclear Receptor ◽  
Cyproterone Acetate ◽  
Transcriptional Activity ◽  
Differential Modulation ◽  
Partial Agonists ◽  
Receptor Action

Antiandrogens are widely used agents in the treatment of prostate cancer, as inhibitors of AR (androgen receptor) action. Although the precise mechanism of antiandrogen action is not yet elucidated, recent studies indicate the involvement of nuclear receptor co-repressors. In the present study, the regulation of AR transcriptional activity by N-CoR (nuclear receptor co-repressor), in the presence of different ligands, has been investigated. Increasing levels of N-CoR differentially affected the transcriptional activity of AR occupied with either agonistic or antagonistic ligands. Small amounts of co-transfected N-CoR repressed CPA (cyproterone acetate)- and mifepristone (RU486)-mediated AR activity, but did not affect agonist (R1881)-induced AR activity. Larger amounts of co-transfected N-CoR repressed AR activity for all ligands, and converted the partial agonists CPA and RU486 into strong AR antagonists. In the presence of the agonist R1881, co-expression of the p160 co-activator TIF2 (transcriptional intermediary factor 2) relieved N-CoR repression up to control levels. However, in the presence of RU486 and CPA, TIF2 did not functionally compete with N-CoR, suggesting that antagonist-bound AR has a preference for N-CoR. The AR mutation T877A (Thr877→Ala), which is frequently found in prostate cancer and affects the ligand-induced conformational change of the AR, considerably reduced the repressive action of N-CoR. The agonistic activities of CPA- and hydroxyflutamide-occupied T877A-AR were hardly affected by N-CoR, whereas TIF2 strongly enhanced their activities. These results indicate that lack of N-CoR action allows these antiandrogens to act as strong agonists on the mutant AR.

scholarly journals Differential Modulation of Androgen Receptor-mediated Transactivation by Smad3 and Tumor Suppressor Smad4

2002 ◽  
Vol 277 (46) ◽  
pp. 43749-43756 ◽  
Author(s):  
Hong-Yo Kang ◽  
Ko-En Huang ◽  
Shiuh Young Chang ◽  
Wen-Lung Ma ◽  
Wen-Jye Lin ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Tumor Suppressor ◽  
Differential Modulation

scholarly journals Androgens and androgen receptor action in skin and hair follicles

2018 ◽  
Vol 465 ◽  
pp. 122-133 ◽  
Author(s):  
Julieta María Ceruti ◽  
Gustavo José Leirós ◽  
María Eugenia Balañá
Keyword(s):  
Androgen Receptor ◽  
Hair Follicles ◽  
Receptor Action

scholarly journals Differential modulation of the androgen receptor for prostate cancer therapy depends on the DNA response element

2020 ◽  
Vol 48 (9) ◽  
pp. 4741-4755
Author(s):  
Steven Kregel ◽  
Pia Bagamasbad ◽  
Shihan He ◽  
Elizabeth LaPensee ◽  
Yemi Raji ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Cancer Progression ◽  
Target Genes ◽  
Normal Growth ◽  
Differential Modulation ◽  
Expression Of Genes ◽  
Prostate Cancer Therapy ◽  
Specific Factors

Abstract Androgen receptor (AR) action is a hallmark of prostate cancer (PCa) with androgen deprivation being standard therapy. Yet, resistance arises and aberrant AR signaling promotes disease. We sought compounds that inhibited genes driving cancer but not normal growth and hypothesized that genes with consensus androgen response elements (cAREs) drive proliferation but genes with selective elements (sAREs) promote differentiation. In a high-throughput promoter-dependent drug screen, doxorubicin (dox) exhibited this ability, acting on DNA rather than AR. This dox effect was observed at low doses for multiple AR target genes in multiple PCa cell lines and also occurred in vivo. Transcriptomic analyses revealed that low dox downregulated cell cycle genes while high dox upregulated DNA damage response genes. In chromatin immunoprecipitation (ChIP) assays with low dox, AR binding to sARE-containing enhancers increased, whereas AR was lost from cAREs. Further, ChIP-seq analysis revealed a subset of genes for which AR binding in low dox increased at pre-existing sites that included sites for prostate-specific factors such as FOXA1. AR dependence on cofactors at sAREs may be the basis for differential modulation by dox that preserves expression of genes for survival but not cancer progression. Repurposing of dox may provide unique opportunities for PCa treatment.

scholarly journals Small Molecule Inhibitors as Probes for Estrogen and Androgen Receptor Action

2010 ◽  
Vol 286 (6) ◽  
pp. 4043-4048 ◽  
Author(s):  
David J. Shapiro ◽  
Chengjian Mao ◽  
Milu T. Cherian
Keyword(s):  
Androgen Receptor ◽  
Small Molecule ◽  
Small Molecule Inhibitors ◽  
Receptor Action
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