Regulation of cell proliferation through a KIT‐mediated mechanism in benign prostatic hyperplasia

Abstract

We investigated the role of the KIT-mediated mechanism in benign prostatic hyperplasia (BPH), and discuss the pathophysiology of BPH and a candidate target of BPH medical therapy. We performed RT-PCR, Western blotting, and immunohistochemistry to examine the expression of KIT in the prostate using a human prostate stromal cell line (PrSC) and human prostate. To investigate the pathophysiological function of KIT, the effects of KIT ligand, stem cell factor (SCF), and imatinib mesylate on cell proliferation were investigated using PrSC. Additionally, we compared the expression level and distribution of KIT in normal prostate and BPH of humans to clarify the contribution of KIT to the pathogenesis of BPH. KIT was expressed in PrSC and human prostate, indicating that these samples are suitable for examining the function of KIT. Immunohistochemical analysis demonstrated that KIT was localized in interstitial cells (ICs) of the stromal component in human prostate. Administration of imatinib mesylate dose-dependently inhibited cell proliferation of PrSC with downregulation of JAK2 and STAT1, which are the main pathways downstream of SCF/KIT signal. SCF promoted cell proliferation of PrSC with upregulation of JAK2 and STAT1. KIT expression and the number of KIT-positive ICs in BPH were found to be significantly larger than in normal prostate. This is the first report to suggest that KIT regulates cell proliferation in the prostate and plays a significant role in the pathophysiology of BPH. Our study may lead to a greater understanding of the mechanism of BPH and provide a therapeutic target.