The Potential Role of Integrin Regulation by Par6 in TGF-beta-induced Apoptosis

dc.contributor.advisorViloria-Petit, Alicia
dc.contributor.authorAvery-Cooper, Geordon James
dc.date.accessioned2011-08-25T21:29:47Z
dc.date.available2011-08-25T21:29:47Z
dc.date.copyright2011-08
dc.date.created2011-08-18
dc.date.issued2011-08-25
dc.degree.departmentDepartment of Biomedical Sciencesen_US
dc.degree.grantorUniversity of Guelphen_US
dc.degree.nameMaster of Scienceen_US
dc.degree.programmeBiomedical Sciencesen_US
dc.description.abstractThe Par6-polarity pathway regulates breast cancer metastasis, and more recently has been shown to regulate transforming growth factor β (TGFβ)-induced apoptosis. Integrins may mediate the regulation of TGFβ-induced apoptosis by Par6, as they are key regulators of cell polarity, survival and death. First, we confirmed that blocking Par6 activation significantly inhibits TGFβ-induced apoptosis in both monolayer and three-dimensional NMuMG (Normal Murine Mammary Gland) cell culture models. TGFβ altered the expression of β1 and β4 integrins in NMuMG monolayers. In addition, TGFβ significantly reduced the basal localization of α6 and β4 integrins in NMuMG three-dimensional acini-like structures (p < 0.001), which was dependent on both Par6 and TGFβ receptor I (TβRI)/SMAD activation. We went on to show that the activities of integrin pro-survival signaling mediators, NF-κB and FAK, were altered in response to TGFβ, and that blocking Par6 activation in the Par6/S345A mutant maintained polarity and basal α6 and β4 integrin expression in the presence of TGFβ in NMuMG three-dimensional structures, in addition to a significant increase in FAK activation. This suggests that TGFβ alters the expression, localization and downstream signaling of integrins, which may contribute to TGFβ-induced apoptosisen_US
dc.identifier.urihttp://hdl.handle.net/10214/2874
dc.language.isoenen_US
dc.publisherUniversity of Guelphen_US
dc.rights.licenseAll items in the Atrium are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectPar6en_US
dc.subjectPolarityen_US
dc.subjectapoptosisen_US
dc.subjectTGF-betaen_US
dc.titleThe Potential Role of Integrin Regulation by Par6 in TGF-beta-induced Apoptosisen_US
dc.typeThesisen_US

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