Effects of androgen receptor degradation by PROTAC ARCC-32 on gene expression in LN95 prostate cancer cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171045 | GEO | 2021/03/30
REPOSITORIES: GEO
Similar Datasets
Project description:Effects of androgen receptor degradation by PROTAC ARCC-32 on gene expression in LN95 prostate cancer cells
| PRJNA718238 | ENA
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
Project description:The goal of this experiment was to compare the gene expression programs mediated by androgen/AR vs. constitutively active, truncated AR variants in castration-resistant CWR-R1 prostate cancer cells. Because constitutive activity of truncated AR variants can mask androgen/AR target genes, the androgen/AR transcriptional program was assessed by silencing the trucnated AR 1/2/3/CE3 variant with siRNA targeting AR exon CE3 and treating cells with vehicle (ethanol) or 1nM DHT. Similarly, because full-length AR activity can mask truncated AR variant target genes, the AR variant transcriptional program was assessed under castrate conditions by selectively silencing full-length AR with siRNA targeting AR exon 7, and comparing this profile with CWR-R1 cells transfected wtih siRNA targeting AR exon 1, which silences all AR expression (full-length and truncated AR variants).
2012-10-23 | GSE41784 | GEO
Project description:Prostate cancer patients undergoing androgen deprivation therapy almost invariably develop castration-resistant prostate cancer. Resistance occurs when mutations in the androgen receptor (AR) render anti-androgen drugs ineffective or when constitutively active splice variants lacking the androgen binding domain entirely (e.g. ARV7) is expressed. In this study, we are reporting the discovery of novel AR-NTD covalent inhibitor 1‐chloro‐3‐[(5‐([(2S)‐3‐chloro‐2‐hydroxypropyl]amino)naphthalen‐1‐yl)amino]propan‐2‐ol (VPC-220010) targeting the AR-N-terminal Domain (AR-NTD). VPC-220010 inhibits AR-mediated transcription of full length and truncated variant ARV7, downregulates AR response genes, and selectively reduces the growth of both full-length AR- and truncated AR-dependent prostate cancer cell lines. We show that VPC-220010 disrupts interactions between AR and its known coactivators and interactors, such as CHD4, FOXA1, ZMIZ1, and several SWI/SNF complex proteins. Taken together, our data suggest that VPC-220010 is a promising small molecule AR-NTD inhibitor for the treatment of CRPC.
2021-07-28 | GSE173331 | GEO
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).
2013-09-01 | GSE49196 | GEO
Project description:Aberrant androgen receptor (AR)-mediated transcription is a critical driver in progression of human prostate cancer. It's known that different doses of androgens can elicit differential transcriptional and proliferative responses in prostate-tumor cells. Here, we set out to examine the androgenic regulation of glycoprotein expression in the membrane fraction of prostate-tumor cells that could serve as mediators or markers of androgen-induced proliferative responses observed in prostate-tumor cells. A bioanalytical workflow involving lectin-affinity chromatography and label-free quantitative mass spectrometry was used to identify androgen-sensitive glycomembrane protein expression associated with androgen-mediated proliferation. This study would facilitate the identification of surface membrane proteins involved in androgen-mediated proliferation and provide potential therapeutic targets in the detection treatment of proliferation prostate-tumors.
2022-03-01 | PXD002913 | Pride
Project description:The spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. Here we identified the cistrome and transcriptome landscape of AR-Vs in CRPC cell lines and determine the clinical significance of AR variants regulated gene.The AR variants binding sites can be identified in 22Rv1 cell line in the absence of androgen. Knocking down full-length AR (AR-FL) doesn't affect AR-Vs binding sites in genome-wide. A set of genes were identified to be regulated uniquely by AR-Vs, but not by AR-FL in androgen-depleted condition. Integrated analysis showed that some genes may be modulated by AR-Vs directly. Unsupervised clustering analysis demonstrated that AR variants gene signature can separate not only the benign and malignant prostate tissue, but also the localized prostate cancer and metastatic CRPC specimens. Some genes modulated uniquely by AR variants were also identified to correlate with the Gleason Pattern of prostate cancer and PSA failure. We conclude that AR spliced variants bind to DNA independent of full-length AR, and can modulate a unique set of genes which is not regulated by full-length AR in the absence of androgen. AR variants gene signature correlate with CRPC and prostate cnacer disease progress. Androgen receptor (AR) binding sites in human prostate cancer 22Rv1 cell lines were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
2014-09-10 | E-GEOD-58478 | biostudies-arrayexpress
Project description:Androgen receptor variant 7 (AR-V7) has been proposed to have independent functional roles different from full length AR. Here we study the functional roles of AR-V7 in chemotherapy castration resiatnt prostate cancer models by ChIp-sequencing approaches.
2023-01-12 | GSE214332 | GEO
Project description:The goal of this experiment was to compare the gene expression programs mediated by androgen/AR vs. constitutively active, truncated AR variants in castration-resistant CWR-R1 prostate cancer cells. Because constitutive activity of truncated AR variants can mask androgen/AR target genes, the androgen/AR transcriptional program was assessed by silencing the trucnated AR 1/2/3/CE3 variant with siRNA targeting AR exon CE3 and treating cells with vehicle (ethanol) or 1nM DHT. Similarly, because full-length AR activity can mask truncated AR variant target genes, the AR variant transcriptional program was assessed under castrate conditions by selectively silencing full-length AR with siRNA targeting AR exon 7, and comparing this profile with CWR-R1 cells transfected wtih siRNA targeting AR exon 1, which silences all AR expression (full-length and truncated AR variants). CWR-R1 cells were maintained under castrate conditions in long term culture in order to enrich for the population of cells harboring a 48kb intragenic deletion in AR intron 1. These late-passage CWR-R1 cells were electroporated with siRNAs targeting AR exon 1, AR exon 7, or AR exon CE3. Electroporated cells were seeded in RPMI 1640 medium containing antibiotics and 5% charcoal-stripped, steroid-depleted medium and allowed to recover for 48h. After this 48h recovery, electroporated cells were switched to serum-free RPMI 1640 with 1nM DHT or 0.1% ethanol (vehicle control) for an additional 24h prior to extraction of total RNA. Three independent biological replicates were performed.
2012-10-23 | E-GEOD-41784 | biostudies-arrayexpress
Project description:The spliced variant forms of androgen receptor (AR-Vs) have been identified recently in castration-resistant prostate cancer (CRPC) cell lines and clinical samples. Here we identified the cistrome and transcriptome landscape of AR-Vs in CRPC cell lines and determine the clinical significance of AR variants regulated gene.The AR variants binding sites can be identified in 22Rv1 cell line in the absence of androgen. Knocking down full-length AR (AR-FL) doesn't affect AR-Vs binding sites in genome-wide. A set of genes were identified to be regulated uniquely by AR-Vs, but not by AR-FL in androgen-depleted condition. Integrated analysis showed that some genes may be modulated by AR-Vs directly. Unsupervised clustering analysis demonstrated that AR variants gene signature can separate not only the benign and malignant prostate tissue, but also the localized prostate cancer and metastatic CRPC specimens. Some genes modulated uniquely by AR variants were also identified to correlate with the Gleason Pattern of prostate cancer and PSA failure. We conclude that AR spliced variants bind to DNA independent of full-length AR, and can modulate a unique set of genes which is not regulated by full-length AR in the absence of androgen. AR variants gene signature correlate with CRPC and prostate cnacer disease progress.
2014-09-10 | GSE58478 | GEO