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Unknown,Transcriptomics,Genomics,Proteomics

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Glucocorticoid Receptor and Androgen Receptor DNA binding in LREX'

ABSTRACT: LREX' are a LnCAP/AR subline with natural expresison of the glucocorticoid receptor. We used the model to compare the AR and GR cistromes in prostate tissue. We determined the GR cistrone in the presence of Dex (100nM) treatment and the AR cistrome in the presene of DHT (1nM) treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Bic MSKCC

PROVIDER: E-GEOD-51497 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Glucocorticoid receptor confers resistance to antiandrogens by bypassing androgen receptor blockade.

Arora Vivek K VK Schenkein Emily E Murali Rajmohan R Subudhi Sumit K SK Wongvipat John J Balbas Minna D MD Shah Neel N Cai Ling L Efstathiou Eleni E Logothetis Chris C Zheng Deyou D Sawyers Charles L CL

Cell 20131201 6

The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. Here, we identify induction of glucocorticoid receptor (GR) expression as a common feature of drug-resistant tumors in a credentialed preclinical model, a finding also confirmed in patient samples. GR substituted for the androgen receptor (AR) to activate a similar but distinguishable set of target genes and was necessary for maintenance of the resistant phenotype. The GR agonist ...[more]

PMID: 24315100

Similar Datasets

Glucocorticoid Receptor and Androgen Receptor DNA binding in LREX'

Project description:LREX' are a LnCAP/AR subline with natural expresison of the glucocorticoid receptor. We used the model to compare the AR and GR cistromes in prostate tissue.

2013-12-27 | GSE51497 | GEO

The knockdown of maternal glucocorticoid receptor mRNA alters embryo development in zebrafish

Project description:In zebrafish, ovulated oocytes contain both cortisol deposited from the maternal circulation and maternal mRNA for the glucocorticoid receptor (gr mRNA), which is spread as granular structures throughout the central ooplasm. At the 1-cell stage (0.2 hpf), this transcript is relocated by streamers in the blastodisc area and equally partitioned among blastomeres. At 15 hpf, it is replaced by the zygotic transcript. Morpholino knockdown was applied to block translation (grATG1MO or MO2-nr3c1 and grATG2MO or MO3-nr3c1) of both maternal and zygotic gr transcripts, while a missplicing morpholino (grmismMO or MO4-nr3c1) was used to block post-transcriptionally the zygotic transcript alone. MO2-nr3c1 and MO3-nr3c1 (but not MO4-nr3c1) treatment produced craniofacial and caudal malformations in 1-dpf embryos and 5-dpf larvae, which were also affected by pericardial oedema, persistent yolk sac, reduced subintestinal veins, altered neurogenesis and uninflated swim bladder. Such effects were rescued with trout gr2 mRNA. Pangenomic microarray analysis revealed that 114 and 37 highly expressed transcripts were up- and down-regulated, respectively, by maternal GR protein deficiency in 5-hpf embryos. Similar alterations were found at 10 hpf. These effects were confirmed by real-time PCR of 2 up- (casp8, grp1 and igf2a) and 1 down-regulated transcripts (mcm6) evaluated at 4, 8 and 12 hpf. As the contents of transcripts were modified already at 4 hpf, it seems that the lack of GR affects both ways the molecular machinery for the degradation of maternal mRNAs. These results indicate that the maternal gr transcript participates in the maternal programming of zebrafish development. MO2-nr3c1 morphants were compared with MO2-nr3c1-5m morphants at 5 hpf and 10 hpf. MO2-nr3c1 morphants were compared with wild type (WT) at 5 hpf and 10 hpf. MO2-nr3c1 is a morpholino selected to knockdown translation of gr mRNA. MO2-nr3c1-5m is a specific control morpholino.

2011-11-16 | E-GEOD-25517 | biostudies-arrayexpress

Androgen and Glucocorticoid stimulation of LREX' cells in vitro

2013-12-27 | GSE51871 | GEO

Androgen and Glucocorticoid stimulation of LREX' cells in vitro

2013-12-27 | E-GEOD-51871 | biostudies-arrayexpress

Cole Lab Fred- genotypeRA experiment

Project description:Mammalian lung development during the saccular and alveolar stages is dependent upon antagonistic molecular signalling by endogenous retinoic acid (RA) and glucocorticoids (GCs) which regulate gene expression via the retinoic acid receptor (RAR) family and the glucocorticoid receptor (GR), respectively. The genomic mechanism of this antagonism was investigated with in vitro distal lung explant cultures from E18.5 GR-null (GR-/-) mice treated with all-trans-RA (atRA) for 2h . Whole mouse genome microarray analysis from lung explant tissue identified a small number of gene targets which were not only significantly induced by atRA in the wildtype lung, but also significantly stimulated to levels greater than atRA-treated wildtype lungs in GR-/- lungs.

2014-01-12 | E-MEXP-3833 | biostudies-arrayexpress

TALEN-Engineered AR Gene Rearrangements Reveal Endocrine Uncoupling of Androgen Receptor in Prostate Cancer

Project description:This experiment addressed the question of whether full length Androgen receptor and Androgen Receptor variant ARv567es have similar transciptional activities. The transcriptomes of R1-AD1, a AR full length expressing cell line, are compared in an AR on (1nM DHT) to an AR off (ethanol vehicle) state. R1-D567 was derived from R1-AD1 and modified with TALENs in such a way as to express only AR-V567es. The AR on and off states were induced with a control siRNA (AR on) or a siRNA targeting exon 1 (AR off). R-AD1 was cultured for 24 hours in either base RPMI media with 1nM DHT or ethanol vehichle and RNA extracted. R1-D567 cells were electroporated with control siRNA or siRNA targeting exon 1 of AR and allowed to recover 48 hours and then cultured in base media with 1nM DHT or ethanol for 24 hrs. Each conditon was done in triplicate.

2013-09-01 | E-GEOD-49196 | biostudies-arrayexpress

Zebrafish transcriptomics in 24 and 36 hpf embryos after knockdown of glucocorticoid receptor translation

Project description:To further characterize the roles of cortisol signaling via the glucocorticoid receptor (GR) in developing zebrafish, we have used morpholino oligonucleotides to knockdown GR protein translation and measured gene expression in RNA extracted from 24 and 36 hours post fertilization (hpf) embryos. The GR morpholino was characterized previously in Nesan et al., 2012, Endocrinology 181, 35-44) Single-cell zebrafish embryos were microinjected with either active morpholino or mispair control. Embryos were frozen at 24 and 36 hpf and total RNA extracted for microarray analysis. Three independent replicates (different breeding events on separate days) were performed for each treatment per timepoint.

2013-08-28 | E-GEOD-50376 | biostudies-arrayexpress

Transcription profiling of human PC3 cells transfected with androgen receptor treated with various concentration of androgens

Project description:We compared PC3 cells with or without harboring the wild-AR construct in the growth conditions of 1nM R1881, 10nM R1881 and ethanol (the solvent for R1881). The MOCK control is PC3 cells transfected with the empty vectors. Experiment Overall Design: 2 PC3 Samples transfected with empty vector, without R1881, 2 PC3 Samples transfected with AR, treated with Ethanol, 2 PC3 Samples transfected with AR, treated with 1nM R1881, 1 PC3 transfected with AR, treated with 10nM R1881.

2009-03-15 | E-GEOD-15091 | biostudies-arrayexpress

LNCAP/AR and a LnCAP/AR subline (LREX') with acquired resistance to 2nd generation antiandrogens

2013-12-27 | GSE51873 | GEO

LNCAP/AR and a LnCAP/AR subline (LREX') with acquired resistance to 2nd generation antiandrogens

Project description:The treatment of advanced prostate cancer has been transformed by novel antiandrogen therapies such as enzalutamide. Using the LnCaP/AR xenograft model, we identified induction of glucocorticoid receptor (GR) expression as a common feature of drug resistant tumors. From a resistant xenograft tumor, we derived a GR expressing resistant subline called LREX' which maintains the resistant phenotype. mRNA expression was used to characterize resistant tissues. LnCaP/AR cells were injected into castrate mice and tumors were established. Mice were then treated with vehicle (Con), 4 days of anti-androgen (ARN-509 10mgkg), or were maintained on anti-androgen (10mg/kg ARN-509 or enzalutamide) until emergence of resistance. Resistant tissues continued to be exposed to anti-androgen through time of harvest. LREX' (LnCaP/AR Resistant to Enzalutamide Xenograft Derived) was derived from an enzalutamide resistant xenograft and was re-injected into castrate mice undergoing continual treatment with enzalutamide. The GR probe on the Illumina array failed to detect GR expression. Therefore, GR expression as determined by qPCR is annotated separately. Of the 10 control tissues, 8 were analyzed twice (technical duplicates annotated as A and B).

2013-12-27 | E-GEOD-51873 | biostudies-arrayexpress

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