In:
Endocrinology, The Endocrine Society, Vol. 150, No. 8 ( 2009-08-01), p. 3576-3583
Abstract:
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 α(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-β signaling cascade. The heterodimeric protein clusterin (apolipoprotein J) was also identified as a prominent node in the network. Responsiveness of TGF-β 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.
Type of Medium:
Online Resource
ISSN:
0013-7227
,
1945-7170
DOI:
10.1210/en.2008-1782
Language:
English
Publisher:
The Endocrine Society
Publication Date:
2009
detail.hit.zdb_id:
2011695-0
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