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Unknown,Transcriptomics,Genomics,Proteomics

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The ETS family member GABPa mediates the development of castrate-resistant prostate cancer

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Silvia Halim

PROVIDER: E-GEOD-49093 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer.

Sharma Naomi L NL Massie Charlie E CE Butter Falk F Mann Matthias M Bon Helene H Ramos-Montoya Antonio A Menon Suraj S Stark Rory R Lamb Alastair D AD Scott Helen E HE Warren Anne Y AY Neal David E DE Mills Ian G IG

Nucleic acids research 20140421 10

In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional ...[more]

PMID: 24753418

Similar Datasets

The ETS family member GABPa mediates the development of castrate-resistant prostate cancer (BeadChip)

Project description:In prostate cancer, the androgen receptor (AR) is a key transcription factor at all disease stages. We recently showed that during progression to castrate-resistant prostate cancer the AR acquires the ability to bind to a distinct set of genomic sites in tissue samples and that some of the genes that are regulated by the AR in these conditions correlate with poor prognosis. Based on this work we hypothesised that the AR is reprogrammed through interactions with other transcription factors. In the present study we show that GABPá, an ETS transcription factor which is upregulated in CRPC, is an AR-interacting transcription factor. Ectopic expression of GABPA in prostate cancer cell-lines enables them to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. Cells were made to either overexpress GABPa or have it knocked down; these conditions also had empty vector and non-targetting controls respectively. All four treatments were carried out with and without androgen for the LNCaP and c42b cell lines. Biological and technical replicates were used.

2014-05-21 | E-GEOD-49083 | biostudies-arrayexpress

The ETS family member GABPa mediates the development of castrate-resistant prostate cancer (ChIP-Seq)

Project description:In prostate cancer, the androgen receptor (AR) is a key transcription factor at all disease stages. We recently showed that during progression to castrate-resistant prostate cancer the AR acquires the ability to bind to a distinct set of genomic sites in tissue samples and that some of the genes that are regulated by the AR in these conditions correlate with poor prognosis. Based on this work we hypothesised that the AR is reprogrammed through interactions with other transcription factors. In the present study we show that GABPÃ¡, an ETS transcription factor which is upregulated in CRPC, is an AR-interacting transcription factor. Ectopic expression of GABPA in prostate cancer cell-lines enables them to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. VCaP prostate cancer cells and Jurkat lymphoma cells were studied for the ETS factors ERG and GABPa binding sites. Each sample was compared to its input.

2014-05-21 | E-GEOD-49091 | biostudies-arrayexpress

Gene expression of LNCaP cells grown in 2D cultures and polyethlene glycol-based hydrogels with the presence of synthetic androgen, R1881

Project description:Analysis of LNCaP cell molecular differences and their response to R1881 in 2D and 3D cultures. Androgen regulated genes were differentially expressed between 2D and 3D cultures. These results provide insights into factors that influence the expression of androgen regulated genes In this study, LNCaP cells cultured in tissue culture plastic (2D) and in the hydrogel (3D) were maintained up to 3 days and 24 days respectively in serum containing media before they were androgen-starved for 48 hours. Cells were either treated with 1nM R1881 or continued to be androgen-deprived (without R1881 with 0.008% ethanol) for another 48 hours prior to cell harvest for gene expression analysis. Biological triplicates were prepared for each condition.

2013-02-04 | E-GEOD-33610 | biostudies-arrayexpress

Transcription profiling of human PC3 cells transfected with androgen receptor treated with various concentration of androgens

Project description:We compared PC3 cells with or without harboring the wild-AR construct in the growth conditions of 1nM R1881, 10nM R1881 and ethanol (the solvent for R1881). The MOCK control is PC3 cells transfected with the empty vectors. Experiment Overall Design: 2 PC3 Samples transfected with empty vector, without R1881, 2 PC3 Samples transfected with AR, treated with Ethanol, 2 PC3 Samples transfected with AR, treated with 1nM R1881, 1 PC3 transfected with AR, treated with 10nM R1881.

2009-03-15 | E-GEOD-15091 | biostudies-arrayexpress

Gene expression of LNCaP cells grown in polyethlene glycol-based hydrogels alone (monocultures) and grown with human osteoblasts as tissue engineered bone (co-culture) with the presence of synthetic androgen, R1881

Project description:Analysis of LNCaP cell molecular differences in monocultures and in co-cultures in the presence of R1881. Human osteoblast molecular signatures were also identified from the tissue engineered bone monocultures. LNCaP cells molecular profile was altered by co-culturing with human osteoblasts compared to LNCaP monocultures with or without R1881 stimulations. These results provide insights into the behavioral change of LNCaP cells in a bone-like microenvironment. In this study, LNCaP cells cultured in the hydrogel were prepared and co-cultured with or without human osteoblasts (in the form oftissue engineered bone). Similarly, tissue engineered bone monocultures were also prepared 4-6 weeks earlier before co-culturing with the LNCaP cells. These cultures were maintained up to 24 days in RPMI growth media (+10% FBS) before they were androgen-starved for 48 hours. Cells were either treated with 1nM R1881 or continued to be androgen-deprived (without R1881 with 0.008% ethanol) for another 48 hours prior to cell harvest for gene expression analysis. Biological triplicates were prepared for each condition.

2014-05-13 | E-GEOD-44143 | biostudies-arrayexpress

Transcription profiling of human LNCaP cells Androgen-starved treated with gedunin and androgen, androgen alone, or vehicle alone for 24h

Project description:Gedunin is a natural product that affects LNCaP androgen-signalling by 24h; We used microarrays to detail the androgen-responsive program of gene expression affected by gedunin treatment at 24h Experiment Overall Design: LNCaP cells were grown to 50% confluency and deprived of androgen, and subsequently treated with gedunin plus androgen, androgen alone, or vehicle alone for 24h prior to direct Trizol lysis and RNA isolation

2008-06-13 | E-GEOD-5508 | biostudies-arrayexpress

Transcription profiling of human androgen starved LNCaP cells treated with celastrol and androgen, androgen alone, or vehicle alone for 24h

Project description:celastrol is a natural product that affects LNCaP androgen-signalling by 24h; We used microarrays to detail the androgen-responsive program of gene expression affected by celastrol treatment at 24h Experiment Overall Design: LNCaP cells were grown to 50% confluency and deprived of androgen, and subsequently treated with celastrol plus androgen, androgen alone, or vehicle alone for 24h prior to direct Trizol lysis and RNA isolation

2008-11-07 | E-GEOD-5507 | biostudies-arrayexpress

Chromatin immunoprecipitation of human LNCaP cells treated with synthetic androgen R1881 or ethanol (vehicle) using androgen receptor antibody

Project description:LNCaP cells were grown in charcoal stripped media for 48hrs and then treated for 1hr with the synthetic androgen R1881 or ethanol (vehicle). Cell extracts from both treatment conditions were then subjected to chromatin-immunoprecipitation using an anti-androgen receptor antibody, before labeling and hybridisation to a microarray containing 24,000 gene promoter regions.

2007-08-17 | E-TABM-233 | biostudies-arrayexpress

Context dependent regulatory patterns of the androgen receptor and androgen receptor target genes

Project description:An investigation of conditions for differentiation of prostate basal epithelial cells including the effect of exogenous Androgen Receptor expression.

2015-10-01 | E-MTAB-3715 | biostudies-arrayexpress

Fine mapping of androgen regulated genes in LNCaP cells

Project description:Detailed analysis of androgen regulated gene expression in the LNCaP prostate cancer cell line. Since androgens and the AR are known to be important for prostate cancer cell proliferation and invasion we aimed to identify androgen receptor (AR) regulated genes by combining this detailed Illumina beadarray study of androgen regulated gene expression with AR ChIP-sequencing data. LNCaP cells were grown in RPMI medium supplemented with 10% charcoal dextran stripped (steroid depleted) FBS for 72h, before treatment with 1nM R1881 or vehicle control. Total RNA was harvested every 30min for 4h and then every hour up to 24h using trizol (Sigma), quantified using a Nanodrop spectrophotometer (ND-1000). RNA samples were prepared for analysis on Illumina Human 6 v2 BeadArrays and Biotrove Realtime PCR panels according to the manufacturers protocols (see Supplementary Methods for details). Expression array data were normalised in R using the beadarray software and BASH (see Supplementary Methods for details) (Cairns et al., 2008; Dunning et al., 2007). 48 total RNA samples from LNCaP cells grown for 72h in RPMI supplemented with 10% charcoal dextran stripped FBS, comprising: 3 time zero samples; 10 vehicle (ethanol) control samples taken at 2h, 4h, 8h, 12h, 24h in duplicate; 36 androgen (R1881) treated samples taken every 30min for 4h then every hour until 24h following treatment (with replicates at 1h, 2h, 4h, 8h, 12h, 16h, 20h, 24h) The Illumina HumanWG v2 BeadArrays consist of two replicate sections that we treat as technical replicate arrays for the purposes of this analysis due to small but systematic shifts between sections that need to be addressed in the normalization. Data were analysed from the raw bead-level using the beadarray software, with spatial artefacts identified and removed automatically (BASH) and curated manually (Cairns et al., 2008; Dunning et al., 2007)

2010-09-01 | E-GEOD-18684 | biostudies-arrayexpress

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