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dc.contributor.authorApostoli, Anthony J.
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2014-08-01 14:15:35.432en
dc.date.accessioned2014-08-06T17:54:46Z
dc.date.issued2014-08-06
dc.identifier.urihttp://hdl.handle.net/1974/12347
dc.descriptionThesis (Ph.D, Pathology & Molecular Medicine) -- Queen's University, 2014-08-01 14:15:35.432en
dc.description.abstractPrevious studies with peroxisome proliferator-activated receptor (PPAR)γ heterozygous mice suggest PPARγ normally suppresses 7,12-dimethylbenz[a]anthracene (DMBA)-induced breast tumour progression, but the mechanisms and cell types involved remain unknown. This thesis elucidates the mammary epithelial role of PPARγ during DMBA- and multi-risk factor (DMBA+protumourigenic high fat diet (ProHF))-mediated breast tumourigenesis. Studies were performed using nulliparous mammary epithelial (MG) cell- and postlactational mammary secretory epithelial (MSE) cell-targeted PPARγ knockout (KO) mice. Surprisingly, the first study revealed that PPARγ-MG KOs had decreased DMBA-induced mammary tumourigenesis compared to congenic wildtype (PPARγ-WT) controls. In contrast, cotreatment with a PPARγ activator was protective in PPARγ-WTs, but worsened breast tumour progression in PPARγ-MG KOs. In the second study, MSE-targeted PPARγ deletion generated a significantly increased protumourigenic mammary gland microenvironment and enhanced DMBA-mediated breast tumourigenesis, suggestive of critical epithelial-stromal cell crosstalk. Cotreatment with a PPARγ activator was protective in PPARγ-WT but not PPARγ-MSE KOs during DMBA- induced mammary tumourigenesis, suggesting critical antibreast cancer signaling within MSEs is PPARγ-dependent. In the third study, DMBA+ProHF treatment significantly increased primary breast tumourigenesis in PPARγ-WTs and lung metastases among PPARγ-MSE KOs. Cotreatment with a PPARγ activator was protective only among PPARγ-WTs. Collectively, these data unveil PPARγ expression and signaling in MG and MSE cells as a candidate prognostic and predictive biomarker for breast cancer, and add further support for the novel chemotherapeutic role of PPARγ activation for a subpopulation of breast cancer patients.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectKnockout Mouse Modelen_US
dc.subjectChemical Carcinogenesisen_US
dc.subjectBreast canceren_US
dc.subjectMammary Epithelial Cellsen_US
dc.subjectMammary Secretory Epithelial Cellsen_US
dc.subjectPPARγen_US
dc.titleThe Mammary Epithelial Contribution Of PPARγ In Breast Tumourigenesisen_US
dc.typeThesisen_US
dc.description.restricted-thesisPlease note we are requesting the archival copy of this thesis file be restricted until such time as the remainder of his manuscripts are accepted for publication. We understand that this will limit the archival copy of the thesis from placement in QSpace, Library and Archives Canada, and ProQuest, and restrict copies of the thesis submitted to the School of Graduate Studies from binding, microfilming or deposit in any library. We also understand this restriction has a maximum 5 year time limit, and will endeavour to release the thesis from restriction as quickly as possible.en
dc.description.degreePh.Den
dc.contributor.supervisorNicol, Christopher J.en
dc.contributor.departmentPathology and Molecular Medicineen
dc.embargo.terms1825en
dc.embargo.liftdate2019-08-05


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