A Role for Estrogen Receptor β in the Inhibition of Prostate Cancer Cell Growth

Persistent Link:
http://hdl.handle.net/10150/221291
Title:
A Role for Estrogen Receptor β in the Inhibition of Prostate Cancer Cell Growth
Author:
Ibragimov, Angela
Affiliation:
The University of Arizona College of Medicine - Phoenix
Issue Date:
30-Apr-2012
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.
Collection Information:
This item is part of the College of Medicine - Phoenix Scholarly Projects 2012 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.
Publisher:
The University of Arizona.
Abstract:
Prostate cancer (PC) and benign prostatic hypertrophy (BPH) are highly prevalent neoplasms. Studies have demonstrated the androgen-dependent nature of benign and pathologic growth of prostate cells. Although Androgen Receptors (AR) have strong proliferative activity in the prostate, recent studies have implicated an anti-proliferative role for Estrogen Receptor Beta (ERβ). This study investigates the effects of ERβ stimulation on normal prostate growth in vivo as well as on PC cell growth in vitro to better elucidate a mechanism for the proposed anti-proliferative actions of ERβ. We also study the interplay between concurrent androgen and ERβ stimulation on PC cell proliferation in vitro. Our hypothesis is that ERβ activation will decrease cell growth and increase cell death in PC cells. Three different ERβ-simulating compounds were analyzed; the selective ERβ agonist diarylpropionitrile (DPN), the dihydrotestosterone (DHT) metabolite 5 alpha androstane-3 β 17b diol (3β-diol), and the isoflavone metabolite, equol, a daidzein-derived compound with phytoestrogen properties. DPN (2mg/Kg) treatment of adult male EZC3 mice for 21 days caused a significant decrease in dorsolateral lobe weight as 4 compared to control (P=.0002). Equol has the same effect on the dorsolateral lobe weight of Sprague-Dawley rats. Furthermore, DPN treatment of human Lymph Node Carcinoma of the Prostate cells (LNCaP) decreased cell proliferation, an effect that was overcome by concurrent treatment with DHT. Interestingly, equol also showed an anti-proliferative effect in cells when used alone as well as in the presence of DHT. 3β-diol, however, did not alter cell growth. Prostate specific antigen (PSA) levels measured from treated LNCaP cells as a measure of androgen stimulation demonstrated that DPN does not interfere with the ability of DHT to stimulate the AR. Furthermore, in vitro data strongly suggest an antagonistic action of equol on the effects of DHT not seen by DPN or 3β-diol. Our data suggest an anti-proliferative role of some ERβ agonists, notably DPN and equol. Although these agonists are ligands of the same receptor, it appears that they activate different molecular pathways and have varying effects on androgen stimulation by DHT. The effects of ERβ agonists are of paramount importance in modulating hormone-induced PC cell proliferation and may have future clinical implication in this widely-prevalent disease condition.
MeSH Subjects:
Prostate Neoplasms; Cell Growth Processes; Estrogen Receptor beta
Description:
A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.
Mentor:
Handa, Robert, PhD

Full metadata record

DC FieldValue Language
dc.language.isoen_USen_US
dc.titleA Role for Estrogen Receptor β in the Inhibition of Prostate Cancer Cell Growthen_US
dc.contributor.authorIbragimov, Angelaen_US
dc.contributor.departmentThe University of Arizona College of Medicine - Phoenixen_US
dc.date.issued2012-04-30-
dc.rightsCopyright © 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.en_US
dc.description.collectioninformationThis item is part of the College of Medicine - Phoenix Scholarly Projects 2012 collection. For more information, contact the Phoenix Biomedical Campus Library at pbc-library@email.arizona.edu.en_US
dc.publisherThe University of Arizona.en_US
dc.description.abstractProstate cancer (PC) and benign prostatic hypertrophy (BPH) are highly prevalent neoplasms. Studies have demonstrated the androgen-dependent nature of benign and pathologic growth of prostate cells. Although Androgen Receptors (AR) have strong proliferative activity in the prostate, recent studies have implicated an anti-proliferative role for Estrogen Receptor Beta (ERβ). This study investigates the effects of ERβ stimulation on normal prostate growth in vivo as well as on PC cell growth in vitro to better elucidate a mechanism for the proposed anti-proliferative actions of ERβ. We also study the interplay between concurrent androgen and ERβ stimulation on PC cell proliferation in vitro. Our hypothesis is that ERβ activation will decrease cell growth and increase cell death in PC cells. Three different ERβ-simulating compounds were analyzed; the selective ERβ agonist diarylpropionitrile (DPN), the dihydrotestosterone (DHT) metabolite 5 alpha androstane-3 β 17b diol (3β-diol), and the isoflavone metabolite, equol, a daidzein-derived compound with phytoestrogen properties. DPN (2mg/Kg) treatment of adult male EZC3 mice for 21 days caused a significant decrease in dorsolateral lobe weight as 4 compared to control (P=.0002). Equol has the same effect on the dorsolateral lobe weight of Sprague-Dawley rats. Furthermore, DPN treatment of human Lymph Node Carcinoma of the Prostate cells (LNCaP) decreased cell proliferation, an effect that was overcome by concurrent treatment with DHT. Interestingly, equol also showed an anti-proliferative effect in cells when used alone as well as in the presence of DHT. 3β-diol, however, did not alter cell growth. Prostate specific antigen (PSA) levels measured from treated LNCaP cells as a measure of androgen stimulation demonstrated that DPN does not interfere with the ability of DHT to stimulate the AR. Furthermore, in vitro data strongly suggest an antagonistic action of equol on the effects of DHT not seen by DPN or 3β-diol. Our data suggest an anti-proliferative role of some ERβ agonists, notably DPN and equol. Although these agonists are ligands of the same receptor, it appears that they activate different molecular pathways and have varying effects on androgen stimulation by DHT. The effects of ERβ agonists are of paramount importance in modulating hormone-induced PC cell proliferation and may have future clinical implication in this widely-prevalent disease condition.en_US
dc.typeThesisen_US
dc.subject.meshProstate Neoplasmsen_US
dc.subject.meshCell Growth Processesen_US
dc.subject.meshEstrogen Receptor betaen_US
dc.descriptionA Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.en_US
dc.contributor.mentorHanda, Robert, PhDen_US
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