VAT-1 is a novel pathogenic factor of progressive benign prostatic hyperplasia.

BACKGROUND:Benign prostatic hyperplasia (BPH), arising from prostatic stromal hyperplasia (STH), is a progressive disease associated with bothersome lower urinary tract symptoms (LUTS). The mechanism of this STH remains unclear because there is no suitable model to study BPH pathology. Previously, we reported a new experimental BPH model that is clinically relevant to STH (the STH model). To elucidate prostatic STH mechanism, we used a compound found to be effective in the STH model. METHODS:A binding protein specific for the effective compound in the STH model was pulled down using a compound-conjugated affinity matrix and identified by mass spectrometry. The RNA interference method was used to confirm the participation of the binding protein in cell proliferation. The binding protein expression in the prostate was assessed by immunohistochemistry. RESULTS:A benzimidazole derivative (Benz) significantly suppressed growth of implanted urogenital sinuses (UGS; 37.1%) in the STH model and inhibited the proliferation of human prostate stromal cells (PrSC) in a concentration-dependent manner (IC50  = 0.43 µM). Vesicle amine transport protein-1 (VAT-1) was identified as a specific binding protein of Benz. Immunohistochemical analysis showed that the VAT-1 expression level was higher in both epithelial and stromal cells of rat UGS and human BPH tissue than in normal prostate. VAT-1 siRNA markedly inhibited proliferation of PrSC, two androgen-independent prostate cancer cell lines (PC3 and DU145), and suppressed UGS growth (28.2%) in the STH model. CONCLUSIONS:Here, we demonstrate that VAT-1 is a novel pathogenic factor in BPH associated with cell proliferation.

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