Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

62 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Bypass mechanisms of the AR pathway in castration-resistant PC346 prostate cancer cells

ABSTRACT: Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for invasive tumors. However, despite initial remission, the cancer will inevitably recur. The present study was set to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions Microarray technology was used to analyze differences in gene expression between androgen-responsive and hormone-refractory prostate cancer cell lines. As model system, we used the androgen-responsive PC346C cells and its castration-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. These sublines were derived from the parental PC346C by long-term androgen ablation (PC346DCC), supplemented with the antiandrogen hydroxyflutamide (PC346Flu1 and PC346Flu2). Previous studies revealed distinct AR modifications in all three castration-resistant sublines: AR overexpression (PC346Flu1), AR down-regulation (PC346DCC) and T877A AR mutation (PC346Flu2). Each of the hormone-refractory sublines were cultured in their respective selection medium (steroid-stripped medium for PC346DCC, supplemented with 1 mM OH-Flutamide for PC346Flu1 and Flu2) and hybridized on the microarrays, together with the parental androgen-responsive PC346C (cultured in complete medium supplemented with 0.1 nM R1881). To account for the biological variability and dye-preferential binding to oligonucleotides on the microarray, four replicate arrays were performed per cell line, using two independent cell passages in dye-swap.

ORGANISM(S): Homo sapiens

SUBMITTER: Rute Marques

PROVIDER: E-GEOD-21596 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

Modulation of Androgen Receptor Signaling in Hormonal Therapy-Resistant Prostate Cancer Cell Lines

Project description:Prostate epithelial cells depend on androgens for survival and function. In early prostate cancer, besides survival, androgens also regulated tumor growth, which is exploited by androgen ablation/ blockade therapies in metastatic disease. The aim of the present study was to characterize the role of the androgen receptor pathway in prostate cancer progression and to identify potential disease markers. Microarray analysis was used to establish the androgen-regulated gene expression profile, upon stimulation with the synthetic androgen R1881 or the antiandrogen hydroxyflutamide, of the androgen-responsive PC346C cell line and its derivative castration-resistant sublines: PC346DCC (vestigial AR levels), PC346Flu1 (AR overexpression) and PC346Flu2 (T877A mutated AR) PC346C, PC346DCC, PC346Flu1 and PC346Flu2 were stimulated with 1 nM R1881, 1uM hydroxyflutamide or vehicle control, following a 4, 8 and 16h time-course. Each condition was performed in dye-swap, using biological duplicates. PC346DCC was only stimulated with R1881, not hydroxyflutamide.

2011-08-04 | E-GEOD-22914 | biostudies-arrayexpress

Bypass mechanisms of the AR pathway in castration-resistant PC346 prostate cancer cells

Project description:Prostate cancer is initially dependent on androgens for survival and growth, making hormonal therapy the cornerstone treatment for invasive tumors. However, despite initial remission, the cancer will inevitably recur. The present study was set to investigate how androgen-dependent prostate cancer cells eventually survive and resume growth under androgen-deprived and antiandrogen supplemented conditions Microarray technology was used to analyze differences in gene expression between androgen-responsive and hormone-refractory prostate cancer cell lines. As model system, we used the androgen-responsive PC346C cells and its castration-resistant sublines: PC346DCC, PC346Flu1 and PC346Flu2. These sublines were derived from the parental PC346C by long-term androgen ablation (PC346DCC), supplemented with the antiandrogen hydroxyflutamide (PC346Flu1 and PC346Flu2). Previous studies revealed distinct AR modifications in all three castration-resistant sublines: AR overexpression (PC346Flu1), AR down-regulation (PC346DCC) and T877A AR mutation (PC346Flu2).

2010-10-21 | GSE21596 | GEO

Modulation of Androgen Receptor Signaling in Hormonal Therapy-Resistant Prostate Cancer Cell Lines

2011-08-05 | GSE22914 | GEO

Androgen receptor DNA binding in response to different ligands across three prostate cancer cell lines

Project description:We performed AR ChIP-seq in LNCaP-AR, VCaP and CWR22PC cells in the presence of vehicle, androgen, or androgen plus antiandrogen. These three cell lines showed variable sensitivity to these drugs.

2015-10-01 | GSE62442 | GEO

Long-term androgen withdrawal and treatment (R1881) of LNCaP-FGC prostate cancer cells

Project description:LNCaP cells were cultures in steroid depleted medium for 5 days before treatment with synthetic androgen (R1881, 10nM) for 16h. Transcriptomics analysis was performed to compare gene expression changes induced by androgen withdrawal or androgen treatment. Genome-wide transcriptomic analysis of LNCaP cells grown in steroid depleted medium, normal (steroid-containing) medium and R1881 treated cells was performed using the Agilent platform

2013-10-22 | E-GEOD-51460 | biostudies-arrayexpress

GREB1 amplifies androgen receptor output in prostate cancer and contributes to antiandrogen resistance

Project description:Genomic amplification of the androgen receptor (AR) is an established mechanism of antiandrogen resistance in prostate cancer. Here we show that the magnitude of AR signaling output, independent of AR genomic alteration or expression level, also contributes to antiandrogen resistance, through upregulation of the coactivator GREB1. We demonstrate 100-fold heterogeneity in AR output within cell lines and show that cells with high AR output have reduced sensitivity to enzalutamide. Through transcriptomic and shRNA knockdown studies, together with analysis of clinical datasets, we identify GREB1 as a gene responsible for high AR output. We show that GREB1 is an AR target gene that amplifies AR output by enhancing AR DNA binding and promoting p300 recruitment. GREB1 knockdown in high AR output cells restores enzalutamide sensitivity in vivo. Thus, GREB1 is a candidate driver of enzalutamide resistance through a novel feed forward mechanism.

2019-02-27 | GSE120720 | GEO

GREB1 amplifies androgen receptor output in prostate cancer and contributes to antiandrogen resistance

2019-02-27 | GSE120680 | GEO

Linking prostate cancer cell AR heterogeneity to distinct castration and Enzalutamide responses

Project description:Molecular mechanisms underlying resistance to androgen deprivation therapy (ADT) and, in particular, to antiandrogen Enzalutamide, in treating castration-resistant prostate cancer (CRPC), remain incompletely understood. Through screening >120 CRPC patient samples, we observed 3 expression patterns of androgen receptor (AR) protein: primarily nuclear (nuc-AR), mixed nuclear/cytoplasmic expression (nuc/cyto-AR), and low/no expression (AR-/lo). Xenograft CRPC modeling in 4 models (i.e., LNCaP, VCaP, LAPC4, and LAPC9) recapitulated the 3 AR expression patterns in castration-resistant tumors developed from parental androgen-dependent tumors. Strikingly, although the 3 CRPC models that retained AR expression (LNCaP, VCaP, and LAPC4) responded, to different levels and in different kinetics, to Enzalutamide, the AR-/lo LAPC9 CRPC was completely refractory to Enzalutamide. By combining whole-genome RNA-Seq and biochemical analyses together with experimental combinatorial therapy in the LNCaP and LAPC9 models, we identified BCL-2 as a critical therapeutic target in both AR+/hi and AR-/lo, Enzalutamide-resistant CRPC models.

2018-08-01 | GSE88752 | GEO

IGR_U693_AR_GE_STUDY

Project description:The androgen receptor is a steroid receptor belonging to the superfamily of hormone-activated transcriptional factors, displaying distinct expression profiles in Sertoli cells during testis development, tightly correlated to the stages of spermatogenesis.The aim of the project was to better understand the AR signaling pathways, and identify androgen regulated genes in a mature Sertoli cell line (ST38c). In order to identify androgen regulated candidate genes we compared the gene expression of mature Sertoli cells (ST38c) in the absence (condition B) and in the presence of a androgenic ligand, dihydrotestosterone (condition ST). In order to understand the AMH gene repression in mature Sertoli cells, which occurs at puberty, soon after the augmentation of the AR expression, we also compared the gene profile of an immature, not expressing the androgen receptor, prepubertal Sertoli cell line (SMAT1-condition A) with the mature Sertoli cell line (ST38c- condition C), expressing the androgen receptor. The Sertoli cell line SMAT1 has been obtaiend from a 6-day old transgenic male mouse (using the targeted oncogenesis SV40). This cell line has been kindly provided to us by Dr Jean Yves Picard (UMR 782), Universite Paris Sud. (Dutertre M, et al., Mol Cell Endocrinol. 1997 Dec 31;136(1):57-65. PMID 9510068).The Sertoli cell line ST38c was obtained in the INSERM U-693 from 8-wk-old male murine testis; from a transgenic mouse carrying the construct in which the SV40 large T Antigen (TAg) was placed under the control of the human vimentin promoter. The development and description of this new cell line have not yet been published.

2014-07-01 | E-MTAB-1732 | biostudies-arrayexpress

Characterization of AR interactome in prostate cancer cells after MC3324 treatment

Project description:We here investigated the alterations in the androgen receptor (AR) itneractome after treatment with the dual-KDM inhibitor MC3324.

2022-10-13 | PXD029249 | Pride

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