GEO DataSets

(Submitter supplied) Treatment induced-resistance of CRPC is an imminent undesirable outcome in patients. Tissue and lineage-specific super-enhancers (SEs) determine cell fate and plasticity during development and disease respectively. However, the identity and function of CRPC-specific SEs (CSEs) regulated genes is unknown. Herein we report the lysine 13 acetylation of the prostate-enriched transcription factor HOXB13 (acK13-HOXB13) mediated by the histone acetyl transferase (HAT) CBP/p300 as a critical mechanism of CSE establishment. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21290

5 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) To understand the mechanistic role of HOXB13 lysine acetylation in CRPC development andd progression, differential gene expression analysis was performed following RNA-sequencing of the HOXB13K13A mutant versus the isogenic parental C4-2B to identify bonafide transcriptional targets of acetylated HOXB13. Chromatin remodeling and self-renewal genes were significantly impacted as a result of HOXB13-K13 mutation. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

5 Samples

Download data: TXT

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

Organism:

Homo sapiens

Type:

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

Platforms:

GPL21290 GPL24676

17 Samples

Download data

(Submitter supplied) While tissue and lineage-specific super-enhancers (SEs) regulate cell fate decision during development, the nature of Castration Resistant Prostate Cancer (CRPC)-specific SEs (CSEs) that drive resistance to AR-targeted therapies is unknown. Herein we report the lysine 13 (K13)-acetylation of Homeodomain transcription factor HOXB13 as a critical feature underlying CSE exclusivity. The histone acetyltransferase (HAT) CBP/p300 specifically acetylates HOXB13 (acK13-HOXB13) in prostate cancer cells. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21290

7 Samples

Download data: BIGWIG, NARROWPEAK

(Submitter supplied) While tissue and lineage-specific super-enhancers (SEs) regulate cell fate decision during development, the nature of Castration Resistant Prostate Cancer (CRPC)-specific SEs (CSEs) is unknown. Herein we report the lysine 13 (K13) acetylation of HOXB13 mediated by the histone acetyltransferase CBP/p300 regulates prostate tumor autonomy. The acK13-HOXB13 shadows H3K27ac at lineage specific SEs and surpasses it at CSEs. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL24676

1 Sample

Download data: H5

(Submitter supplied) The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. more...

Organism:

Homo sapiens

Type:

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

Platforms:

GPL20301 GPL11154

40 Samples

Download data: BEDGRAPH, BW, TXT

(Submitter supplied) We uncovered a novel acetylation event at Lys609 in the Zinc finger DNA binding domain of AR (acK609-AR) that altered global transcription program, bestowing insensitivity for enzalutamide and abiraterone. ACK1 kinase small molecule inhibitor, (R)-9b not only curbed K609-acetylation, but also significantly compromised enzalutamide-resistant CRPC tumor growth.

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL21290

6 Samples

Download data: NARROWPEAK

(Submitter supplied) We identified BRD4 as an epigenetic regulator of the prostate lineage specific gene HOXB13 during progression of the disease from an androgen dependent to an androgen independent state.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18460

9 Samples

Download data: TXT

(Submitter supplied) We identified BRD4 as an epigenetic regulator of the prostate lineage specific gene HOXB13 during progression of the disease from an androgen dependent to an androgen independent state.

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL18460

2 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) 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) Androgen-deprivation therapy is a standard treatment for advanced prostate cancer. However, most patients eventually acquire resistance and progress to castration-resistant prostate cancer (CRPC). In this study, we established new CRPC cell lines, AILNCaP14 and AILNCaP15, from LNCaP cells under androgen-deprived conditions. Unlike most pre-existing CRPC cell lines, both cell lines expressed higher levels of androgen receptor (AR) and prostate-specific antigen (PSA) than parental LNCaP cells. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

24 Samples

Download data: XLSX

(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) 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) The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor–related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR–ROR response element (RORE) to stimulate AR gene transcription. more...

Organism:

Homo sapiens

Type:

Genome binding/occupancy profiling by high throughput sequencing

Platform:

GPL11154

16 Samples

Download data: BEDGRAPH

(Submitter supplied) The androgen receptor (AR) is overexpressed and hyperactivated in human castration-resistant prostate cancer (CRPC). However, the determinants of AR overexpression in CRPC are poorly defined. Here we show that retinoic acid receptor–related orphan receptor γ (ROR-γ) is overexpressed and amplified in metastatic CRPC tumors, and that ROR-γ drives AR expression in the tumors. ROR-γ recruits nuclear receptor coactivator 1 and 3 (NCOA1 and NCOA3, also known as SRC-1 and SRC-3) to an AR–ROR response element (RORE) to stimulate AR gene transcription. more...

Organism:

Homo sapiens

Type:

Expression profiling by high throughput sequencing

Platform:

GPL11154

6 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) 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