Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Differential expression in LNCaP cells expressing the wild-type androgen receptor (AR-WT) or the ligand-independent AR-V7 splice variant

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE71336 | GEO | 2016/02/01

SECONDARY ACCESSION(S): PRJNA290916

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

miRNA differential expression in LNCaP cells expressing the wild-type androgen receptor (AR-WT) or the ligand-independent AR-V7 splice variant

Project description:Constitutively active AR variants are truncated proteins lacking the c-terminal region containing the ligand binding domain (LBD) and the activation function 2 (AF-2). The expression of these AR variants in CRPC was also associated with the resistance to novel therapies such as enzalutamide and abiraterone acetate. These variants are also involved in tumor progression.

2016-02-01 | GSE71335 | GEO

mRNA differential expression in LNCaP cells expressing the wild-type androgen receptor (AR-WT) or the ligand-independent AR-V7 splice variant

2016-02-01 | GSE71334 | GEO

Expression profiling by RNA-seq of LNCaP cells expressing wild-type androgen receptor (AR-WT), AR-V7 splice variant or mutant AR-Q641X

Project description:The androgen receptor (AR) signaling remains the key therapeutic target in metastatic prostate cancer (PCa). However, development of castration resistant PCa is frequently observed and can be in part attributed to the expression of mutant AR variants, which lack the ligand binding domain and are thus constitutively active. These constitutive AR variants have been associated with castration resistance but also with tumor progression. However, little data is available regarding their transcriptional activities. In this study, we depicted the transcriptional landscapes of the two constitutive AR variants AR-Q641X and AR-V7 by whole transcriptome sequencing and Gene Set Enrichment Analysis.

2020-11-01 | GSE158557 | GEO

Cistrome and transcriptome analysis identifies unique androgen receptor (AR) and AR-V7 splice variant chromatin binding and transcriptional activities.

Project description:The constitutively active androgen receptor (AR) splice variant, AR-V7, plays an important role in resistance to androgen deprivation therapy in castration resistant prostate cancer (CRPC). Studies seeking to determine whether AR-V7 is a partial mimic of the AR, or also has unique activities, and whether the AR-V7 cistrome contains unique binding sites have yielded conflicting results. One limitation in many studies has been the low level of AR variant compared to AR. Here, LNCaP and VCaP cell lines in which AR-V7 expression can be induced to match the level of AR, were used to compare the activities of AR and AR-V7. The two AR isoforms shared many targets, but overall had distinct transcriptomes. Optimal induction of novel targets sometimes required more receptor isoform than classical targets such as PSA. The isoforms displayed remarkably different cistromes with numerous differential binding sites. Some of the unique AR-V7 sites were located proximal to the transcription start sites (TSS). A de novo binding motif similar to a half ARE was identified in many AR-V7 preferential sites and, in contrast to conventional half ARE sites that bind AR-V7, FOXA1 was not enriched at these sites. This supports the concept that the AR isoforms have unique actions with the potential to serve as biomarkers or novel therapeutic targets.

| S-EPMC8969163 | biostudies-literature

Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC)

Project description:This SuperSeries is composed of the SubSeries listed below.

2021-01-21 | GSE143907 | GEO

Androgen receptor and its splice variant, AR-V7, differentially induce mRNA splicing in prostate cancer cells.

Project description:Prostate cancer (PCa) is dependent on the androgen receptor (AR). Advanced PCa is treated with an androgen deprivation therapy-based regimen; tumors develop resistance, although they typically remain AR-dependent. Expression of constitutively active AR variants lacking the ligand-binding domain including the variant AR-V7 contributes to this resistance. AR and AR-V7, as transcription factors, regulate many of the same genes, but also have unique activities. In this study, the capacity of the two AR isoforms to regulate splicing was examined. RNA-seq data from models that endogenously express AR and express AR-V7 in response to doxycycline were used. Both AR isoforms induced multiple changes in splicing and many changes were isoform-specific. Analyses of two endogenous genes, PGAP2 and TPD52, were performed to examine differential splicing. A novel exon that appears to be a novel transcription start site was preferentially induced by AR-V7 in PGAP2 although it is induced to a lesser extent by AR. The previously described AR induced promoter 2 usage that results in a novel protein derived from TPD52 (PrLZ) was not induced by AR-V7. AR, but not AR-V7, bound to a site proximal to promoter 2, and induction was found to depend on FOXA1.

| S-EPMC7809134 | biostudies-literature

Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC) [RNA-seq]

Project description:CRPC remains AR dependent. There are multiple mechanisms for reactivation of AR including expression of constitutively active AR splices variant AR-V7 (AR3). Earlier studies suggest that though the variants regulate many of the same genes as AR, they also have unique targets. Another argument is that the variant is a “weak” AR. We have used an LNCaP cell line that expresses AR-V7 in response to doxycycline (LNCaP AR-V7) to compare the activities of the two isoforms and to identify differential regulation of target genes. We also used VCaP cell line that expresses AR-V7 in response to doxycycline (VCaP AR-V7) to validate the activities of the two isoforms in an alternative prostate cancer cell line. The transcriptomes for AR and AR-V7 in these cell lines were identified using RNA-Seq.

2021-01-21 | GSE143905 | GEO

Androgen Receptor splice variant V7 (AR-V7) mediates AR signalling in castration resistant prostate cancer (CRPC) [ChIP-exo]

Project description:CRPC remains AR dependent. There are multiple mechanisms for reactivation of AR including expression of constitutively active AR splices variant AR-V7 (AR3). Earlier studies suggest that though the variants regulate many of the same genes as AR, they also have unique targets. Another argument is that the variant is a “weak” AR. We have used an LNCaP cell line that expresses AR-V7 in response to doxycycline to compare DNA interactions of the two isoforms and to identify differential regulation of target genes. ChIP-exo method was used to map AR and AR-V7 interaction with DNA in LNCaP engineered cell line (LNCaP AR-V7) at single base resolution.

2021-07-07 | GSE143906 | GEO

The RNA-binding protein Sam68 regulates expression and transcription function of the androgen receptor splice variant AR-V7.

Project description:Castration-resistant (CR) prostate cancer (PCa) partly arises due to persistence of androgen receptor (AR) transcriptional activity in the absence of cognate ligand. An emerging mechanism underlying the CRPCa phenotype and predicting response to therapy is the expression of the constitutively-active AR-V7 splice variant generated by AR cryptic exon 3b inclusion. Here, we explore the role of the RNA-binding protein (RBP) Sam68 (encoded by KHDRBS1), which is over-expressed in clinical PCa, on AR-V7 expression and transcription function. Using a minigene reporter, we show that Sam68 controls expression of exon 3b resulting in an increase in endogenous AR-V7 mRNA and protein expression in RNA-binding-dependent manner. We identify a novel protein-protein interaction between Sam68 and AR-V7 mediated by a common domain shared with full-length AR, and observe these proteins in the cell nucleoplasm. Using a luciferase reporter, we demonstrate that Sam68 co-activates ligand-independent AR-V7 transcriptional activity in an RNA-binding-independent manner, and controls expression of the endogenous AR-V7-specific gene target UBE2C. Our data suggest that Sam68 has separable effects on the regulation of AR-V7 expression and transcriptional activity, through its RNA-binding capacity. Sam68 and other RBPs may control expression of AR-V7 and other splice variants as well as their downstream functions in CRPCa.

| S-EPMC4550848 | biostudies-literature

α-Mangostin Promotes In Vitro and In Vivo Degradation of Androgen Receptor and AR-V7 Splice Variant in Prostate Cancer Cells.

Project description:A major limitation of current prostate cancer pharmacotherapy approaches is the inability of these compounds to target androgen receptor variants or mutants that develop during prostate cancer progression. The demand for novel therapeutics to prevent, slow, and treat prostate cancer is significant because FDA approved anti-androgens are associated with adverse events and can eventually drive drug-resistant prostate cancer. This study evaluated α-mangostin for its novel ability to degrade the androgen receptor and androgen receptor variants. α-Mangostin is one of more than 70 isoprenylated xanthones isolated from Garcinia mangostana that we have been evaluating for their anticancer potential. Prostate cancer cells treated with α-mangostin exhibited decreased levels of wild-type and mutated androgen receptors. Immunoblot, immunoprecipitation, and transfection experiments demonstrated that the androgen receptor was ubiquitinated and subsequently degraded via the proteasome, which we hypothesize occurs with the assistance of BiP, an ER chaperone protein that we have shown to associate with the androgen receptor. We also evaluated α-mangostin for its antitumor activity and promotion of androgen receptor degradation in vivo. In summary, our study demonstrates that androgen receptor degradation occurs through the novel activation of BiP and suggests a new therapeutic approach for prostate cancer.

| S-EPMC10093438 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data