Molecular targets of doxazosin in human prostatic stromal cells

The Prostate
Hongjuan ZhaoDonna M Peehl

Abstract

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). 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. 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.

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Citations

Sep 4, 2009·Naunyn-Schmiedeberg's Archives of Pharmacology·Yi-Fan YangMing-Jai Su
Aug 19, 2011·Cell Death & Disease·J JehleD Thomas
Mar 23, 2013·Journal of Clinical Medicine Research·Georgios PapadopoulosDionisios Mitropoulos
Sep 12, 2009·The American Journal of the Medical Sciences·He-Lin TianYan-Hui Kang
Oct 18, 2006·Journal of Cellular Physiology·Hongjuan ZhaoDonna M Peehl
Oct 17, 2012·Life Sciences·Flávia K DelellaSérgio L Felisbino
Oct 31, 2014·Journal of Molecular Neuroscience : MN·Jian WangChuanlu Jiang

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