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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
8
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pubmed:dateCreated |
2009-7-22
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pubmed:abstractText |
Benign prostatic hyperplasia (BPH) is an age-related disease of unknown etiology characterized by prostatic enlargement and coinciding with distinctive alterations in tissue histomorphology. To identify the molecular mechanisms underlying the development of BPH, we conducted a DNA microarray study using a previously described animal model in which chronic alpha(1)-adrenergic stimulation by repeated administration of phenylephrine evokes histomorphological changes in the rat prostate that resemble human BPH. Bioinformatic tools were applied to microarray data obtained from prostate tissue to construct a network model of potentially relevant signal transduction pathways. Significant involvement of inflammatory pathways was demonstrable, including evidence for activation of a TGF-beta signaling cascade. The heterodimeric protein clusterin (apolipoprotein J) was also identified as a prominent node in the network. Responsiveness of TGF-beta signaling and clusterin gene and protein expression were confirmed independently of the microarray data, verifying some components of the model. This is the first attempt to develop a comprehensive molecular network for histological BPH induced by adrenergic activation. The study also implicated clusterin as a novel biochemical target for therapy.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1945-7170
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
150
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3576-83
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pubmed:dateRevised |
2010-9-27
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pubmed:meshHeading |
pubmed-meshheading:19443575-Adrenergic alpha-Agonists,
pubmed-meshheading:19443575-Animals,
pubmed-meshheading:19443575-Blotting, Western,
pubmed-meshheading:19443575-Cell Line,
pubmed-meshheading:19443575-Gene Expression Profiling,
pubmed-meshheading:19443575-Gene Expression Regulation,
pubmed-meshheading:19443575-Male,
pubmed-meshheading:19443575-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:19443575-Phenylephrine,
pubmed-meshheading:19443575-Phosphorylation,
pubmed-meshheading:19443575-Prostatic Hyperplasia,
pubmed-meshheading:19443575-Rats,
pubmed-meshheading:19443575-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:19443575-Signal Transduction,
pubmed-meshheading:19443575-Smad2 Protein,
pubmed-meshheading:19443575-Transforming Growth Factor beta
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pubmed:year |
2009
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pubmed:articleTitle |
A signaling network in phenylephrine-induced benign prostatic hyperplasia.
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pubmed:affiliation |
Departments of Surgery andBiological Chemistry and Molecular Pharmacology, Harvard Medical School, The Urological Diseases Research Center, Children's Hospital, Boston, Massachusetts 02115, USA. michael.freeman@childrens.harvard.edu
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