DIFFERENTIAL GENE-EXPRESSION OF STEROID 5-ALPHA-REDUCTASE-2 IN-CORE NEEDLE BIOPSIES FROM MALIGNANT AND BENIGN PROSTATIC TISSUE

Androgens are implicated in the development of prostate cancer (CAP) a nd benign prostate hyperplasia. The conversion of testosterone to the more potent metabolite dihydrotestosterone by prostate-specific steroi d 5 alpha-reductase type 2 (5 alpha-red2) is a key mechanism in the ac tion of androgens in the prostate and is important in the promotion an d progression of prostate diseases. Manipulation of the turnover of an drogens is thus fundamental in the pharmacological treatment strategy. We have developed a sensitive solution hybridization method for quant ification of the gene expression of 5 alpha-red2 in core needle biopsi es of the prostate. The 5 alpha-red2-specific messenger RNA (mRNA) lev els were measured in 50 human prostate transrectal ultrasound-guided c ore biopsies obtained from 31 outpatients (median age 72, range 57-88 yr) undergoing biopsy for diagnostic purposes. Significant differences were observed in the gene expression of 5 alpha-red2 between cancerou s and noncancerous tissue. In the 14 biopsies judged cancerous, the me dian 5 alpha-red mRNA levels were 3.5 amol/ng total RNA compared with 12.0 amol/ng total RNA in the biopsies showing no cancer (P = 0.0018). The median 5 alpha-red2 mRNA level in noncancerous tissue was thus 3. 4 times higher than in the cancerous specimens.