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Molecular targets of doxazosin in human prostatic stromal cells

ABSTRACT: BACKGROUND: We used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an alpha(1)-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH). METHODS: Hierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real-time reverse-transcription polymerase chain reaction (RT-PCR). : Hierarchical clustering analyses separated untreated normal and BPH cells. Sixty-seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)-alpha-related activity were identified. CONCLUSIONS: Normal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell-cell signaling/signal transduction, and transcriptional regulation. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Keywords: stimulus_or_stress_design

ORGANISM(S): Homo sapiens

PROVIDER: GSE4010 | GEO | 2006/01/11

SECONDARY ACCESSION(S): PRJNA95103

REPOSITORIES: GEO

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Molecular targets of doxazosin in human prostatic stromal cells

Project description:BACKGROUND: We used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an alpha(1)-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH). METHODS: Hierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real-time reverse-transcription polymerase chain reaction (RT-PCR). : Hierarchical clustering analyses separated untreated normal and BPH cells. Sixty-seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)-alpha-related activity were identified. CONCLUSIONS: Normal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell-cell signaling/signal transduction, and transcriptional regulation. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Computed

2006-01-10 | E-GEOD-4010 | biostudies-arrayexpress

Transcription profiling of doxazosin response in human prostatic stromal cells

Project description:BACKGROUND: We used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an alpha(1)-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH). METHODS: Hierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Hierarchical clustering analyses separated untreated normal and BPH cells. Sixty-seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)-alpha-related activity were identified. CONCLUSIONS: Normal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell-cell signaling/signal transduction, and transcriptional regulation.

2005-11-07 | E-SMDB-2935 | biostudies-arrayexpress

Transcription profiling of doxazosin response, an alpha(1)-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH)

Project description:BACKGROUND: We used cDNA microarray analysis to obtain insights into the mechanisms of action of doxazosin, an alpha(1)-adrenergic receptor antagonist used to treat benign prostatic hyperplasia (BPH). METHODS: Hierarchical clustering analysis and significance analysis of microarray (SAM) were performed to identify genes differentially expressed between untreated stromal cells cultured from normal tissue and BPH, and changes in gene expression induced by doxazosin. Transcript levels of selected genes were validated by real-time reverse-transcription polymerase chain reaction (RT-PCR). RESULTS: Hierarchical clustering analyses separated untreated normal and BPH cells. Sixty-seven genes whose expression varied at least twofold after doxazosin treatment in both normal and BPH cells were identified, as were 93 genes differentially regulated in normal versus BPH cells. Molecular targets consistent with tumor necrosis factor (TNF)-alpha-related activity were identified. CONCLUSIONS: Normal versus BPH stromal cells differ in global gene transcription. Doxazosin induced gene expression changes relevant to proliferation/apoptosis, immune defense, cell-cell signaling/signal transduction, and transcriptional regulation.

2005-11-07 | E-SMDB-2934 | biostudies-arrayexpress

Worms spun in centrifuge at elevated g values

Project description:Worms spun at higher than normal g values for 4 days on 20G centrifuge vs. worms kept at 1 X G. Both are mixed stage cultures. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Physical Characteristics: worms kept at increased g values for 4 days (x g value) stimulus_or_stress_design

2013-06-22 | E-GEOD-38877 | biostudies-arrayexpress

S. typhimurium Bile regulated genes

Project description:Bile treatment 30 and 60 minutes regulation of genes by PmrA and UblA, 30 and 60 minutes A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Keywords: stimulus_or_stress_design

2006-01-06 | GSE3975 | GEO

si RNA interference of Hepatitis B viral gene expression

Project description:Gene expression profiling comparisons of HepG2.2.15 or PLC/PRF/5 cells either mock (M) transfected or transfected with 0.2 microM S2 RNA or Scrambled (SCR) siRNA were carried out in duplicate 48 hours after transfection. The experiments were carried out in duplicate (a and b). The following combinations of RNA were used on 2 slides each: 1. 2.2.15 cells: mock transfection (reference) versus S2 treatment (test) 2. 2.2.15 cells: mock transfection (reference) versus Scr treatment (test) 3. 2.2.15 cells: Scr treatment (reference) versus S2 treatment (test) 4. PLC/PRF/5 cells: mock transfection (reference) versus S2 treatment (test) 5. PLC/PRF/5 cells: mock transfection (reference) versus Scr treatment (test) 6. PLC/PRF/5 cells: Scr treatment (reference) versus S2 treatment (test) A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Keywords: stimulus_or_stress_design

2006-01-07 | GSE3992 | GEO

Molecular features of PDGFRa+ mesenchymal progenitors and progeny in the mammary gland

Project description:We performed RNA-seq on FACS-purified GFP+ and tdTomato+ stromal and luminal mammary populations from untreated and hormone stimulated adult PdgfraCreR26mTmG lineage tracing mice. Unsupervised hierarchical clustering of the top 20% most variable genes resulted in clustering of GFP+ and tdTomato+ stromal subsets into distinct groups. Distance-analysis of DEGs between GFP+ and tdTomato+ fractions in stromal and luminal lineages showed GFP+ stromal cells to have more similar transcriptomes to luminal cells than to tdTomato+ stroma. DEGs between GFP+ and tdTomato+ stromal subsets were enriched in pathways regulating Lysosomes, Focal adhesion, ECM-receptor interaction, Actin cytoskeleton and PI3K-Akt signaling. Hormone stimulation perturbed multiple cancer-associated pathways, as well as Endocytosis, Focal Adhesion and the Phosphatidylinositol System – all important in cell migration.

2019-02-25 | GSE123714 | GEO

Affinity purification of ribosomes and associated RNAs from stress-treated cells

Project description:In this study, we systematically identified ribosome associated RNAs. To identify ribosome associated RNAs, C-terminal ZZ-tagged Rpl16a, expressed under control of its native promoter, was affinity purified from whole cell extracts of cultures grown to mid-log phase. Extracts were incubated with immunoglobulin G (IgG) coupled microbeads, washed, and ribosomes were eluted by tobacco etch virus (TEV) protease treatment. To analyze how changes in steady-state mRNA levels (= transcriptome) are related to changes of respective messages in the translatome, total RNA and ribosome associated RNA from stress-treated and untreated cells were analyzed with yeast cDNA microarrays. To achieve this, fluorescently labeled (Cy5) cDNA was prepared from total RNA isolated from yeast cell extracts and from affinity-purified ribosomes, and each sample was mixed with differentially labeled (Cy3) cDNA prepared from a common reference RNA pool, and competitively hybridized on yeast cDNA microarrays. We performed five independent experiments with untreated cells grown in minimal medium (t=0 reference) and three or more independent biological replicates of treated cells. Altogether, we sampled the cell's response to five different "stress treatments" that were applied for relatively short periods of time (10 or 20 minutes) to avoid secondary effects triggered by transcriptional adaption. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment Time: Duration of the treatment Growth Condition: Type of treatment stimulus_or_stress_design

2010-06-25 | E-GEOD-13653 | biostudies-arrayexpress

Transcription profiling of human prostatic stromal cells cultured from diseased vs normal tissues

Project description:To obtain a comprehensive view of the transcriptional programs in prostatic stromal cells of different histological/pathological origin, we profiled 18 adult human stromal cell cultures from normal transition zone (TZ), normal peripheral zone (PZ), benign prostatic hyperplasia (BPH), and prostate cancer (CA) using cDNA microarrays.

2006-11-06 | E-SMDB-3867 | biostudies-arrayexpress

CCL171, T47D, MDA-MB231 cell lines: stimulation with BMP7 and antagonists

Project description:Methods: We used an ex vivo culture model and measured gene expression changes in human lung fibroblasts after stimulation with BMPs and their antagonists using HEEBO microarrays. The in vitro data were correlated with in vivo observations in published expression datasets of human lung adenocarcinomas. Results: We have systematically analyzed the response to BMP2, BMP4, BMP7 and their antagonists, gremlin and noggin, to define common and specific gene expression patterns. A BMP2 induced gene expression signature was defined, which is specific for stromal fibroblasts. Gene expression profiles from lung adenocarcinoma biopsies were analyzed to determine the prognostic significance of the Fibroblast specific BMP2 induced gene list. This gene list successfully segregated patients with different prognostic outcome in 3 datasets. In a small dataset (Garber et al.) there was a strong trend for a worse prognosis of patients with adenocarcinomas of all stages over-expressing the Fibroblast specific BMP2 induced gene list. In two larger datasets with stage I adenocarcinomas we observed a significantly worse disease-free (p=0.002, Lee et al. and p=0.002, Bhattacharjee et al.) and overall survival (p=0.0002). Conclusions: The effects of BMPs and their antagonists are heterogeneous in different cell types. The gene expression pattern induced by BMP2 in primary lung fibroblasts may predict outcomes of patients with lung adenocarcinomas. A stimulus or stress experiment design type is where that tests response of an organism(s) to stress/stimulus. e.g. osmotic stress, behavioral treatment stimulus_or_stress_design

2016-02-19 | E-GEOD-66108 | biostudies-arrayexpress

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