biomedical and healthCAre Data Discovery Index Ecosystem
biomedical and healthCAre Data Discovery Index Ecosystem
| Title: | Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor β (ERβ) Response to 5α-reductase Inhibition in Prostate Epithelial Cells
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| dateReleased: |
05-12-2016
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| description: |
Current pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor (AR) driven, inflammatory disorder affecting elderly men, include 5α-reductase (5AR) inhibitors (i.e. dutasteride and finasteride) to block the conversion of testosterone to the more potent AR ligand dihydrotestosterone (DHT). Since DHT is the precursor for estrogen receptor β (ERβ) ligands, 5AR inhibitors could potentially limit ERβ activation, which maintains prostate tissue homeostasis. We have uncovered signaling pathways in BPH-derived prostate epithelial cells (BPH-1) that are impacted by 5AR inhibition. The induction of apoptosis and repression of the cell-adhesion protein E-cadherin by the 5AR inhibitor, dutasteride, requires both ERβ and TGFβ. Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative-feedback loop in TGFβ and ERβ signaling pathways as evidenced by the potentiation of apoptosis induced by dutasteride or finasteride upon pharmacological inhibition or shRNA-mediated ablation of COX-2. Concurrently, COX-2 positively impacts ERβ action through its effect on the expression of a number of steroidogenic enzymes in the ERβ-ligand metabolic pathway. Therefore, effective combination pharmacotherapies, which have included non-steroidal anti-inflammatory drugs, must take into account biochemical pathways affected by 5AR inhibition and opposing effects of COX-2 on the tissue protective action of ERβ. Next-generation sequencing (n=3) of shRNA mediated knockdown of COX-2 or scrambled control in BPH-1 prostate epithelial cell line
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| privacy: |
not applicable
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| aggregation: |
instance of dataset
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| ID: |
E-GEOD-80979
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| refinement: |
raw
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| alternateIdentifiers: |
80979
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| keywords: |
functional genomics
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| dateModified: |
05-23-2016
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| availability: |
available
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| types: |
gene expression
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| name: |
Homo sapiens
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80979/E-GEOD-80979.raw.1.zip |
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ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-80979/E-GEOD-80979.processed.1.zip |
| storedIn: |
ArrayExpress
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| qualifier: |
gzip compressed
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| format: |
TXT
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| accessType: |
download
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| authentication: |
none
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| authorization: |
none
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| accessURL: | https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80979 |
| storedIn: |
Gene Expression Omnibus
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| qualifier: |
not compressed
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| format: |
HTML
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| accessType: |
landing page
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| primary: |
true
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| authentication: |
none
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| authorization: |
none
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| abbreviation: |
EBI
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| homePage: | http://www.ebi.ac.uk/ |
| ID: |
SCR:004727
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| name: |
European Bioinformatics Institute
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| homePage: | https://www.ebi.ac.uk/arrayexpress/ |
| ID: |
SCR:002964
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| name: |
ArrayExpress
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