ELUCIDATING THE ROLE OF PRIMARY CILIA AS PUTATIVE TUMOR SUPPRESSORS IN THE PROSTATE AND BREAST

Persistent Link:
http://hdl.handle.net/10150/332325
Title:
ELUCIDATING THE ROLE OF PRIMARY CILIA AS PUTATIVE TUMOR SUPPRESSORS IN THE PROSTATE AND BREAST
Author:
Hassounah, Nadia
Issue Date:
2014
Publisher:
The University of Arizona.
Rights:
Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, 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.
Embargo:
Dissertation not available, per author's request.
Abstract:
Prostate and breast cancer are among the most commonly diagnosed cancers and leading causes of cancer-related deaths in men and women worldwide. It is therefore evident that enhanced understanding of tumorigenesis is required to improve diagnostic tools, improve prognostics and identify novel therapeutic targets. The goal of this dissertation was to elucidate the role of primary cilia in prostate and breast cancer. Little is known about the role primary cilia may play in these cancers. Primary cilia are microtubule-based organelles which aid in sensing the extracellular environment and participate in signal transduction. Important developmental signaling pathways, such as Hedgehog (Hh) and Wnt signaling pathways, involve cilia. These pathways have also been implicated in prostate and breast cancer. In this work, we demonstrate that cilia are lost through prostate cancer progression. The few remaining cilia on prostate cancers appeared to be dysfunctional, as assessed by quantifying cilia lengths, an indirect measure of functionality. We also investigated a link between the observed cilia loss and canonical Wnt signaling in prostate cancers. Primary cilia have been determined to have a suppressive role in Wnt signaling, therefore we predicted loss of cilia to correlate with increased Wnt signaling. A link between cilia loss or shortened cilia and activated Wnt signaling was suggested in a subset of prostate cancers. Our lab has established that cilia are similarly lost in breast cancer. These data suggested the hypothesis that cilia may act as tumor suppressor organelles in the prostate and breast. To test this hypothesis, we knocked down cilia in an oncogenic mammary mouse model and assessed changes in tumor growth and characteristics. We observed enhanced tumor growth with cilia loss. The data supports the hypothesis that primary cilia may be playing a tumor suppressor role in the prostate and breast, and provides promising avenues for identifying novel therapeutic approaches for cancer patients.
Type:
text; Electronic Dissertation
Keywords:
Cancer Biology; Hedgehog Signaling; Primary Cilia; Prostate Cancer; Wnt Signaling; Breast Cancer
Degree Name:
Ph.D.
Degree Level:
doctoral
Degree Program:
Graduate College; Cancer Biology
Degree Grantor:
University of Arizona
Advisor:
McDermott, Kimberly M.

Full metadata record

DC FieldValue Language
dc.language.isoen_USen
dc.titleELUCIDATING THE ROLE OF PRIMARY CILIA AS PUTATIVE TUMOR SUPPRESSORS IN THE PROSTATE AND BREASTen_US
dc.creatorHassounah, Nadiaen_US
dc.contributor.authorHassounah, Nadiaen_US
dc.date.issued2014-
dc.publisherThe University of Arizona.en_US
dc.rightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, 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.releaseDissertation not available, per author's request.en_US
dc.description.abstractProstate and breast cancer are among the most commonly diagnosed cancers and leading causes of cancer-related deaths in men and women worldwide. It is therefore evident that enhanced understanding of tumorigenesis is required to improve diagnostic tools, improve prognostics and identify novel therapeutic targets. The goal of this dissertation was to elucidate the role of primary cilia in prostate and breast cancer. Little is known about the role primary cilia may play in these cancers. Primary cilia are microtubule-based organelles which aid in sensing the extracellular environment and participate in signal transduction. Important developmental signaling pathways, such as Hedgehog (Hh) and Wnt signaling pathways, involve cilia. These pathways have also been implicated in prostate and breast cancer. In this work, we demonstrate that cilia are lost through prostate cancer progression. The few remaining cilia on prostate cancers appeared to be dysfunctional, as assessed by quantifying cilia lengths, an indirect measure of functionality. We also investigated a link between the observed cilia loss and canonical Wnt signaling in prostate cancers. Primary cilia have been determined to have a suppressive role in Wnt signaling, therefore we predicted loss of cilia to correlate with increased Wnt signaling. A link between cilia loss or shortened cilia and activated Wnt signaling was suggested in a subset of prostate cancers. Our lab has established that cilia are similarly lost in breast cancer. These data suggested the hypothesis that cilia may act as tumor suppressor organelles in the prostate and breast. To test this hypothesis, we knocked down cilia in an oncogenic mammary mouse model and assessed changes in tumor growth and characteristics. We observed enhanced tumor growth with cilia loss. The data supports the hypothesis that primary cilia may be playing a tumor suppressor role in the prostate and breast, and provides promising avenues for identifying novel therapeutic approaches for cancer patients.en_US
dc.typetexten
dc.typeElectronic Dissertationen
dc.subjectCancer Biologyen_US
dc.subjectHedgehog Signalingen_US
dc.subjectPrimary Ciliaen_US
dc.subjectProstate Canceren_US
dc.subjectWnt Signalingen_US
dc.subjectBreast Canceren_US
thesis.degree.namePh.D.en_US
thesis.degree.leveldoctoralen_US
thesis.degree.disciplineGraduate Collegeen_US
thesis.degree.disciplineCancer Biologyen_US
thesis.degree.grantorUniversity of Arizonaen_US
dc.contributor.advisorMcDermott, Kimberly M.en_US
dc.contributor.committeememberMcDermott, Kimberly M.en_US
dc.contributor.committeememberBowden. G. Timothyen_US
dc.contributor.committeememberCress, Anneen_US
dc.contributor.committeememberMartinez, Jesseen_US
dc.contributor.committeememberNagle, Raymonden_US
dc.contributor.committeememberRogers, Gregoryen_US
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