Decreased gene expression of steroid 5 alpha-reductase 2 in human prostate cancer: implications for finasteride therapy of prostate carcinoma.
BACKGROUND
Steroid 5alpha-reductase 2 (SRD5A2) catalyzes the conversion of testosterone to the more potent androgen, DHT, in the prostate. The therapeutic influence of SRD5A2 inhibitor finasteride on prostate cancer is currently unknown. The direction and extent of changes in SRD5A2 expression in disease tissues is a relevant issue in this regard.


METHODS
The expression differences of SRD5A2 in tissues representative of normal, benign, and malignant growth in the human prostate were examined in parallel by comparative analysis of relevant microarray gene expression data. Semiquantitative RT-PCR was used to further verify the gene expression differences of SRD5A2.


RESULTS
Consistently decreased expression of SRD5A2 was observed in 25 prostate cancer samples when compared to 25 matched normal samples and nine BPH samples. Expression differences among these samples for six other genes were presented in parallel as indicators of the direction and extent of expression changes. These additional genes include SRD5A1, Hepsin (overexpressed in prostate cancer), AMACR (overexpressed in prostate cancer), Keratin 8 (epithelial marker), smooth muscle actin (stromal marker), Nell2 (overexpressed in BPH). Semiquantitative RT-PCR verified the expression differences for SRD5A2 in six normal, six BPH, and six prostate cancer samples.


CONCLUSIONS
Results from this study, combined with those from previous studies, indicate an association of prostate cancer with reduced 5alpha-reductase enzymatic activity as a result of remarkably decreased expression of the SRD5A2 gene. The implications of this study for finasteride therapy of prostate cancer are discussed.
Luo
Jun
J
Department of Urology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA.
Dunn
Thomas A
TA
Ewing
Charles M
CM
Walsh
Patrick C
PC
Isaacs
William B
WB
D016022:Case-Control Studies; D042944:Cholestenone 5 alpha-Reductase; D030541:Databases, Genetic; D004791:Enzyme Inhibitors / Q000627:therapeutic use; D018120:Finasteride / Q000627:therapeutic use; D015870:Gene Expression; D020869:Gene Expression Profiling / Q000379:methods; D006801:Humans; D008297:Male; D021141:Nucleic Acid Amplification Techniques; D020411:Oligonucleotide Array Sequence Analysis; D010088:Oxidoreductases / Q000037:antagonists & inhibitors / Q000235:genetics*; D011470:Prostatic Hyperplasia / Q000235:genetics; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D004791:Enzyme Inhibitors; D018120:Finasteride; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase