title: Intermediate-conductance Ca2+-activated K+ channel, KCa3.1, as a novel therapeutic target for benign prostatic hyperplasia.
abstract: Recently, a new experimental stromal hyperplasia animal model corresponding to clinical benign prostatic hyperplasia (BPH) was established. The main objective of this study was to elucidate the roles of the intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) in the implanted urogenital sinus (UGS) of stromal hyperplasia BPH model rats. Using DNA microarray, real-time polymerase chain reaction, Western blot, and/or immunohistochemical analyses, we identified the expression of K(Ca)3.1 and its transcriptional regulators in implanted UGS of BPH model rats and prostate needle-biopsy samples and surgical prostate specimens of BPH patients. We also examined the in vivo effects of a K(Ca)3.1 blocker, 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34), on the proliferation index of implanted UGS by measurement of UGS weights and proliferating cell nuclear antigen immunostaining. K(Ca)3.1 genes and proteins were highly expressed in implanted UGS rather than in the normal host prostate. In the implanted UGS, the gene expressions of two transcriptional regulators of K(Ca)3.1, repressor element 1-silencing transcription factor and c-Jun, were significantly down- and up-regulated, and the regulations were correlated negatively or positively with K(Ca)3.1 expression, respectively. Positive signals of K(Ca)3.1 proteins were detected exclusively in stromal cells, whereas they were scarcely immunolocalized to basal cells of the epithelium in implanted UGS. In vivo treatment with TRAM-34 significantly suppressed the increase in implanted UGS weights compared with the decrease in stromal cell components. Moreover, significant levels of K(Ca)3.1 expression were observed in human BPH samples. K(Ca)3.1 blockers may be a novel treatment option for patients suffering from BPH.
authors: Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Muzuhoku, Nagoya 467-8603, Japan.
authors: Susumu
authors: S
authors: Ohya
authors: Satomi
authors: S
authors: Niwa
authors: Yoshiyuki
authors: Y
authors: Kojima
authors: Shoichi
authors: S
authors: Sasaki
authors: Motomu
authors: M
authors: Sakuragi
authors: Kenjiro
authors: K
authors: Kohri
authors: Yuji
authors: Y
authors: Imaizumi