Molecular targets of doxazosin in human prostatic stromal cells.
BACKGROUND
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).


METHODS
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).


RESULTS
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.


CONCLUSIONS
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.
Zhao
Hongjuan
H
Department of Urology, Stanford University School of Medicine, Stanford, California 94305-5118, USA.
Lai
Frank
F
Nonn
Larisa
L
Brooks
James D
JD
Peehl
Donna M
DM
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D017209:Apoptosis; D049109:Cell Proliferation; D017292:Doxazosin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D006801:Humans; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011467:Prostate / Q000502:physiology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D017154:Stromal Cells / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000317:Adrenergic alpha-Antagonists; D014409:Tumor Necrosis Factor-alpha; D017292:Doxazosin