GEO DataSets

(Submitter supplied) Prostate cancer is the most commonly diagnosed and second-most lethal cancer among men in the United States. The vast majority of prostate cancer deaths are due to castration-resistant prostate cancer (CRPC) – the lethal form of the disease that has progressed despite therapies that interfere with activation of androgen receptor (AR) signaling. One emergent resistance mechanism to medical castration is synthesis of intratumoral androgens that activate the AR. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

30 Samples

Download data: TXT

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Other; Expression profiling by high throughput sequencing

Platform:

GPL11154

32 Samples

Download data: TXT

(Submitter supplied) We report RNA sequencing data on serial biopsies of prostate cancer VCaP xenografts as the tumors pass from androgen-sensitivity (Pre-Cx), to castration resistance (CRPC, castration resistant prostate cancer), onto resistance to dual therapy with abiraterone plus enzalutamide (AER). From comparison of these RNAseq data sets, we were able to determine differentially expressed genes between the AER/CRPC and Pre-Cx states that could mediate resistance to androgen deprivation therapies.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

8 Samples

Download data: TXT

(Submitter supplied) Illumina gene array analyses of prostate cancer cell lines that had acquired resistance to Enzalutamide (MDV3100).

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

48 Samples

Download data: TXT

(Submitter supplied) Enzalutamide (formerly MDV3100 and available commercially as Xtandi), a novel androgen receptor (AR) signaling inhibitor, blocks the growth of castration-resistant prostate cancer (CRPC) in cellular model systems and was shown in a clinical study to increase survival in patients with metastatic CRPC. Enzalutamide inhibits multiple steps of AR signaling: (1) binding of androgens to AR, (2) AR nuclear translocation, and (3) association of AR with DNA. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

18 Samples

Download data: CEL, TXT

(Submitter supplied) Competitive inhibitors of acetyl-lysine binding to the bromodomains of the BET (bromodomain and extra terminal) family are being developed for the treatment of solid and heme malignancies. BET family member BRD4 function at enhancers/super-enhancers has been shown to sustain signal-dependent or pathogenic gene expression programs. Here we tested the hypothesis that the transcription factor drivers of castration-resistant prostate cancer (CRPC) clinical progression, including the Androgen Receptor (AR), are critically dependent on BRD4 and thus represent a sensitive solid tumor indication for the BET inhibitor ABBV-075. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

8 Samples

Download data: CEL

(Submitter supplied) Androgen receptor (AR) is required for castration resistant prostate cancer (CRPC) progression, but the function and disease relevance of AR-bound enhancers remain poorly understood. Here, we identify a group of AR-regulated enhancer RNAs (e.g. PSA eRNA) that are upregulated in CRPC cells, patient-derived xenografts (PDX) and patient tissues. PSA eRNA binds to CYCLIN T1, activates P-TEFb and promotes in cis and trans gene transcription by increasing serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p). more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL16791

12 Samples

Download data: BW

(Submitter supplied) Castration resistant prostate cancer (CRPC) is a lethal disease. Sustained aberrant activation of androgen receptor (AR) becomes a central mechanism that contributes to endocrine therapy resistance. Here, we demonstrate that AR-bound enhancer RNAs (AR-eRNAs), including eRNA of the KLK3 (or PSA) gene, are upregulated in human CRPC cells and patient tissues. By enhancing C-termine domain (CTD) serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p), PSA eRNA acts in cis to promote PSA mRNA transcription and in trans to induce mRNA expression of a large set of genes involved in androgen action, cell cycle progression and tumorgenesis. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

18 Samples

Download data: BW

(Submitter supplied) This SuperSeries is composed of the SubSeries listed below.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing; Genome binding/occupancy profiling by high throughput sequencing

Platforms:

GPL11154 GPL16791

36 Samples

Download data: BEDGRAPH, BW, TXT

(Submitter supplied) Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

6 Samples

Download data: BEDGRAPH

(Submitter supplied) Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

4 Samples

Download data: TXT

(Submitter supplied) LNCaP-derived MDV3100-resistant clones were treated with MDV3100 for 24h prior to collection This experiment is designed to see if MDV3100 resistant clones remain responsive to MDV3100

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

40 Samples

Download data: CEL

(Submitter supplied) Genetically engineered LNCaPs overexpressing various AR alleles were treated with 0.1% DMSO or 10uM MDV3100 for 24h prior to collection This experiment is designed to see if expressing the F876L/T877A mutant AR can rescue AR signaling in the presence of MDV3100

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL570

16 Samples

Download data: CEL

(Submitter supplied) Human androgen receptor (AR) is a hormone-activated transcription factor that is an important drug-target in the treatment of prostate cancer. Current small molecule AR-antagonists (such as Enzalutamide) compete with male hormones that bind to the steroid binding pocket of the AR ligand binding domain (LBD). In castration-resistant prostate cancer (CRPC), drug-resistance can manifest through AR-LBD mutations that convert AR-antagonists into agonists, or by expression of AR-variants lacking the LBD. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

7 Samples

Download data: NARROWPEAK

(Submitter supplied) 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. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10904

12 Samples

Download data: TXT

(Submitter supplied) RNA-sequencing of VCaP and LNCaP, LNCaP-EnzR, or LNCaP AR-V7 overexpressing prostate cancer cell lines treated with AR degrader ARD-61.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

26 Samples

Download data: GFF3, XLSX

(Submitter supplied) Enzalutamide (ENZ) is a potent androgen receptor (AR) antagonist with activity in castration-resistant prostate cancer (CRPC); however, progression to ENZ-resistant (ENZ-R) CRPC frequently occurs with rising serum PSA levels, implicating AR full length (ARFL) or variants (AR-Vs) in disease progression. To define functional roles of ARFL and AR-Vs in ENZ-R CRPC, we designed 3 antisense oligonucleotides (ASO) targeting exon 1, intron 1, and exon 8 in AR pre-mRNA to knockdown either ARFL alone, or ARFL plus AR-Vs, and examined their respective effects in LNCaP-derived ENZ-R, as well as M12 and 22Rv1, cells. more...

Organism:

Homo sapiens

Type:

Genome variation profiling by genome tiling array

Platform:

GPL10123

6 Samples

Download data: TXT

(Submitter supplied) RNA-sequencing data of the prostate cancer xenograft PC346C-DCC-K model. Tumor bearing mice were treated daily with Enzalutamide (N=10, 60mg/kg) or placebo (N=5, vehicle) for a period of 7 days. Tumor were subsequently isolated and snap-frozen. Tumor tissue was lysed and homogenized in QIAzol (ref #79306, Qiagen, Hilden, Germany) using an Ultra-Turrax T25 (Janke & Kunkel, Staufen, Germany). Total RNA was isolated using the miRNA-easy mini kit (ref # 217004, Qiagen), and RNA quality was measured using the Bioanalyzer RNA 6000 Nano assay (ref #5067, Agilent, Santa Clara, California, USA). more...

Organism:

Homo sapiens; Mus musculus

Type:

Expression profiling by high throughput sequencing

Platform:

GPL25431

15 Samples

Download data: TXT

(Submitter supplied) Androgen receptor (AR) pathway inhibition remains the cornerstone for first- and second-line prostate cancer therapies. Although AR signaling inhibitors, such as enzalutamide and abiraterone extend survival in recurrent and castration-resistant prostate cancer (CRPC), durable and complete responses are rare. Resistance mechanisms employed by metastatic CRPC include amplification of AR and AR splice variants in AR-positive CRPC (ARPC) and conversion to AR-null phenotypes, such as double-negative prostate cancer (DNPC) and small cell or neuroendocrine prostate cancer (SCNPC). more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platforms:

GPL24676 GPL16791

194 Samples

Download data: TXT

(Submitter supplied) The standard of care for patients with advanced form of prostate cancer, castration-resistant, now includes enzalutamide, a second generation antiandrogen. However, most of the treated patients will develop resistance to enzalutamide based therapy in around a year, succumbing to lethal disease. Investigating the transcriptome of enzalutamide-resistant prostate cancer cell lines, we identified CXCR7 as one of the most upregulated genes suggesting its role in advanced prostate cancer. more...

Organism:

Homo sapiens

Type:

Expression profiling by array

Platform:

GPL10558

10 Samples

Download data: TXT