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A Role for Estrogen Receptor Beta in the Inhibition of Prostate Cancer Cell Growth Angela Ibragimov, Laura Hinds, Robert J

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A Role for Estrogen Receptor Beta in the Inhibition of Prostate Cancer Cell Growth Angela Ibragimov, Laura Hinds, Robert J A Role for Estrogen Receptor β in the Inhibition of Prostate Cancer Cell Growth Item Type text; Electronic Thesis Authors Ibragimov, Angela Publisher The University of Arizona. Rights Copyright © is held by the author. Digital access to this material is made possible by the College of Medicine - Phoenix, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Download date 23/09/2021 15:37:18 Link to Item http://hdl.handle.net/10150/221291 Poster Board # P2-32 A Role for Estrogen Receptor Beta in the Inhibition of Prostate Cancer Cell Growth Angela Ibragimov, Laura Hinds, Robert J. Handa Basic Medical Sciences. University of Arizona College of Medicine, Phoenix, Arizona. Introduction Results Summary and Discussion Prostate cancer and benign prostatic hypertrophy are Summary: highly prevalent pathologies in men and are known to be As expected, DHT increased prostate cell proliferation as indicated by heavily influenced by the degree of androgen exposure. a relative decrease in dead cell population compared to control, suggesting an anti-apoptotic effect. The presence of both androgen receptors (AR) and Furthermore, equol demonstrated anti-proliferative effect in cells when estrogen receptor beta (ERβ) have been well-characterized alone as well as in the presence of DHT. in prostate and in prostate tumor cells. Equol also demonstrated a significant decrease in Rat prostate, ARs have strong proliferative activity in prostate, however, namely the dorsolateral lobe which is known to be the most homologous recent studies have implicated an anti-proliferative role for to the human peripheral zone, the site of most carcinomas. ERβ. DPN treatment of LNCaP cells decreased cell proliferation, an effect that interestingly was overcome by concurrent treatment with DHT. DPN Several compounds have been identified to bind to ERβ, also decreased dorsolateral prostate lobe weight in mice. namely the synthetic ERβ agonist diarylpropionitrile (DPN), 3bdiol did not significantly alter cell growth, but does show an the dihydrotestosterone (DHT) metabolite 5 alpha interesting trend of blocking the anti-apoptotic effect of DHT. androstane-3 beta 17b diol (3bdiol), and the isoflavone Conclusions: metabolite, equol (a daidzein-derived compound with These data suggest an anti-proliferative role of some ERβ agonists, phytoestrogen properties). notably DPN and equol. β Furthermore, in vitro and in vivo data strongly suggest an antagonistic By studying the effects of these ER agonists on normal action of Equol on effects of DHT not seen by DPN. prostate growth in a mouse model and on human Prostate The cellular signaling pathway of ERβ stimulation is not yet clear, but cancer cell growth in vitro, we attempted to elucidate the this data suggest that different agonists of the same receptor likely interplay between concurrent androgen and ERβ stimulation trigger different pathways. on prostate growth and prostate cancer cell proliferation. The anti-androgen effects of Equol are of paramount importance in regulating/counteracting hormone-induced Prostate cancer cell Methods proliferation and may have future clinical implication in this widely- In Vitro Model: LnCaP cells were grown to 80% confluency prevalent disease condition. and were then treated with either 5nM DHT, 10nM 3beta diol, Future Direction 10 nM S-DPN, 20 uM Equol, or Vehicle (ethanol <0.1% in RPMI 1640 media containing charcoal-stripped 10% fetal What are gene expression profiles in prostate cancer cells bovine serum) for 2 days. Live cells and dead cells were following ERβ stimulation +/- DHT? quantified using a Trypan Blue assay. Does ERβ stimulation interfere with androgen receptor In Vivo Model: Adult male EZC3 mice (ages 72-234 days) mediated PSA secretion from human prostate cancer cells? were treated with DPN (n=7, 2mg/Kg BW), Equol (n=6, 10 Does ERβ stimulation prevent the development of mg/kg BW) or vehicle (n=8, 27% beta-cyclodextrin in 0.9% spontaneous prostate tumors in the TRAMP model of prostate cancer? NaCl) for 21 days. Prostate lobes were individually dissected and weighed. Sprague. -Dawley rats from Charles River age 90-100 days old Reference were injected for 10 days with equol (n=5, 10mg/kg) in 1. Carruba, G. (2007). Estrogen and Prostate Cancer: An eclipsed Truth in an Androgen- Dominated Scenario. Journal of Cellular Biochemistry, 102, 899-911. dimethylsulfoxide (DMSO) or with just DMSO (n=3) while fed 2. Chunyan, Z., Dahlman-Wright, K., & Gustafsson, J. (2008). Estrogen Receptor B: an overview and update. Nuclear receptor signaling, 6, e003. with phyto-free diet. 3. Lund, T., Munson, D., Haldy, M., Setchell, K., Lephart, E., & Handa, R. (2003). Equol is a Statistics: All data were analyzed using 1-way or 2 way novel anti-androgen that inhibits prostate growth and hormone feedback. Biology of Reproduction, 70, 1188-1195. ANOVA. Posthoc analysis was performed using Dunnett’s test 4. Takayashi, Y., Lavigne, J., Hursting, S., Chandramouli, G., Perkins, S., Kim, Y., et al. (2006). Molecular Signatures of Soy-Derived Phytochemicals in Androgen-Responsive Prostate Cancer and significant level was set at p<0.05. Cells: A comparison Study Using DNA Microarray. Molecular Carcinogenesis, 45, 943-956. TEMPLATE DESIGN © 2008 www.PosterPresentations.com .
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