Opposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor (ER) Response to 5-reductase Inhibition in Prostate Epithelial Cells
Transcriptomics Dataset
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General Information
AccessionGSE80979
TitleOpposing Effects of Cyclooxygenase-2 (COX-2) on Estrogen Receptor (ER) Response to 5-reductase Inhibition in Prostate Epithelial Cells
DescriptionCurrent pharmacotherapies for symptomatic benign prostatic hyperplasia (BPH), an androgen receptor (AR) driven, inflammatory disorder affecting elderly men, include 5-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 (ER) ligands, 5AR inhibitors could potentially limit ER 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 ER and TGF. Dutasteride also induces cyclooxygenase type 2 (COX-2), which functions in a negative-feedback loop in TGF and ER 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 ER action through its effect on the expression of a number of steroidogenic enzymes in the ER-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 ER.
Landing Pagehttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE80979
RepositoryGene Expression Omnibus
Tools used to analyze the dataset
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ARCHS4
Published September 2017
ARCHS4 provides access to gene counts from HiSeq 2000 and HiSeq 2500 platforms for human and mouse experiments from GEO ...
4645
Clustergrammer
Published October 2017
Web-based tool for visualizing and analyzing high-dimensional data as interactive and shareable heatmaps
4645
Canned Analyses generated with the dataset
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Interactive heatmap visualization of RNA-seq dataset GSE80979
ARCHS4, Clustergrammer
Highly interactive web-based heatmap visualization of the top 500 most variable genes in t...
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