INSULIN-LIKE GROWTH-FACTOR AXIS ABNORMALITIES IN PROSTATIC STROMAL CELLS FROM PATIENTS WITH BENIGN PROSTATIC HYPERPLASIA

Benign prostatic hyperplasia (BPH) is a common proliferative disorder of unknown etiology. To assess whether patients with BPH have alterati ons in their prostatic IGF axis, we measured the expression (by Northe rn blotting) and the production (by Western ligand blotting and RIA) o f insulin-like growth factor-II (IGF-II) and IGF-binding proteins (IGF BPs) in prostatic epithelial and stromal cell strains grown from norma l (n = 7), hyperplastic (n = 7), and malignant (n = 5) surgical specim ens. Levels of IGF-II messenger ribonucleic acid (mRNA; normalized for actin expression) were 10-fold higher in BPH stromal cell strains com pared to those in normal stromal cell strains (P < 0.0001). Western li gand blotting of conditioned medium (CM) from normal stromal cells dem onstrated the presence of IGFBP-2, -3, and -4. In the CM of BPH stroma l cells, IGFBP-2 levels were dramatically reduced to less than 20% of normal (P < 0.001). Additionally, IGFBP-5, which was not observed in s ignificant amounts in normal stromal cell-CM, was found in large quant ities in BPH stromal cell-CM. Northern blot analysis of mRNA from norm al and BPH stromal cells demonstrated a 5-fold decrease in IGFBP-2 mRN A (P < 0.001) and a 4-fold increase in IGFBP-5 mRNA (P < 0.01) in BPH compared to normal cells. In prostate stromal cells from cancer specim ens, no abnormalities were found. No abnormalities were observed in th e IGF axis parameters evaluated in prostate epithelial cells from BPH or cancer strains. We conclude that prostatic stromal cell strains iso lated from patients with BPH hyperexpress the mRNA for IGF-II and IGFB P-5 while expressing reduced amounts of IGFBP-2 mRNA. IGFBP, but not I GF-II, peptide levels in CM correspond to the mRNA differences. This i s the first documentation of altered gene and protein expression in th is common disease. We speculate that these abnormalities in the IGF ax is may be important in the pathogenesis of BPH.