You have accessJournal of UrologyProstate Cancer: Basic Research II1 Apr 2014MP31-08 SEMENOGELIN I PROMOTES PROSTATE CANCER CELL GROWTH VIA FUNCTIONING AS AN ANDROGEN RECEPTOR COACTIVATOR AND PROTECTING AGAINST ZINC CYTOTOXICITY Hitoshi Ishiguro, Koji Izumi, Yi Li, Yichun Zheng, Eiji Kashiwagi, Takashi Kawahara, and Hiroshi Miyamoto Hitoshi IshiguroHitoshi Ishiguro More articles by this author , Koji IzumiKoji Izumi More articles by this author , Yi LiYi Li More articles by this author , Yichun ZhengYichun Zheng More articles by this author , Eiji KashiwagiEiji Kashiwagi More articles by this author , Takashi KawaharaTakashi Kawahara More articles by this author , and Hiroshi MiyamotoHiroshi Miyamoto More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.917AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A seminal plasma protein, semenogelin I (SgI), contributes to semen clotting, upon binding to Zn2+, and can be proteolyzed by prostate-specific antigen (PSA) to release the encased spermatozoa after ejaculation. In contrast to the well-recognized physiological actions of semenogelins, their role in human malignancies remains poorly understood. We have demonstrated that SgI is overexpressed in prostate cancer tissues and its expression is enhanced by zinc treatment in LNCaP cells. In the current study, using cell lines stably expressing SgI, we investigated its biological functions in prostate cancer. METHODS We assessed the effects of SgI, in conjunction with zinc and androgen, on cell growth and androgen receptor (AR) in prostate cancer lines, using western blotting, MTT assay, transwell invasion assay, luciferase assay, and co-immunoprecipitaion assay. RESULTS Even though SgI is a secreted protein, immunoblots detected signals in conditioned medium only after culturing SgI-overexpressing cells, but not control LNCaP with endogenous SgI, suggesting that prostate cancer cells do not generally secrete a large amount of SgI. Zinc, without SgI, inhibited cell growth of both AR-positive and AR-negative lines. Co-expression of SgI induced dihydrotestosterone (DHT)-mediated proliferation of AR-positive cells when cultured with zinc, whereas SgI and/or DHT showed marginal effects in AR-negative cells. Similarly, SgI enhanced DHT-induced cell invasion only in the presence of high-level zinc. Moreover, overexpression of SgI induced DHT-mediated PSA expression in cancer cells, whereas SgI showed marginal induction without DHT. In a reporter gene assay, SgI showed a slight inhibitory effect (15% decrease) at 0 µM zinc, a slight stimulatory effect (31% increase) at 15 µM zinc, or a significant stimulatory effect (3.2-fold) at 100 µM zinc on DHT-enhanced AR transactivation. Co-immunoprecipitation then demonstrated DHT-induced physical interactions between AR and SgI. CONCLUSIONS We show molecular evidence indicating that cellular SgI, as a new AR coactivator, enhances the transcriptional activity of the receptor in the presence of high levels of zinc and promotes androgen-mediated prostate cancer progression. Our results may also provide an underlying reason why prostate cancer tissue contains relatively high levels of zinc which by itself shows an inhibitory effect on tumor growth. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e325 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Hitoshi Ishiguro More articles by this author Koji Izumi More articles by this author Yi Li More articles by this author Yichun Zheng More articles by this author Eiji Kashiwagi More articles by this author Takashi Kawahara More articles by this author Hiroshi Miyamoto More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...