The role of epigenetic changes in chemoresistant breast cancer cells

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dc.contributor.authorFilkowski, Jody
dc.contributor.authorUniversity of Lethbridge. Faculty of Arts and Science
dc.contributor.supervisorKovalchuk, Olga
dc.date.accessioned2012-01-31T18:13:52Z
dc.date.available2012-01-31T18:13:52Z
dc.date.issued2010
dc.degree.disciplineBiological Sciences
dc.degree.fieldArts and Sciences
dc.degree.levelDoctor of Philosophy
dc.degree.subfieldSciences
dc.descriptionxiii, 116 leaves : ill. (some col.) ; 29 cmen_US
dc.description.abstractCytotoxic chemotherapy is extremely important in adjuvant treatment of breast cancer. Yet, tumours frequently acquire chemoresistance that correlates with increased aggressiveness and poor prognosis. Three theories exist describing how the resistance develops: genetic, epigenetic and karyotypic theory. The epigenetic theory is the least explored. Here we analyzed the role of the epigenetic phenomena in the acquisition of drug resistance. To do so, we employed genome wide screens of microRNA and gene expression, DNA methylation and complete genome hybridization. We identified three novel microRNA interactions involved in the chemoresistant phenotype. These three microRNAs displayed depressed expression in the resistant cell lines and we were able to re-establish some level of drug sensitivity through ectopic expression of these under expressed microRNAs. In addition, we described the role of DNA methylation in impacting expression of a wide range of genes, thus, contributing to the phenotype of chemoresistance. Furthermore, we revealed a distorted global DNA methylation pattern that coincides with massive instability of the resistant genome. Finally, our results present a striking similarity between gene expression, epigenetic profiles and chromosomal aberrations in two different drug resistant cell lines. Taken together, this project suggests that the acquisition of chemoresistant phenotype is epigenetic in nature and may arise with a predictable pattern. Elucidating the specifics of this pattern may in the future prove useful in developing treatment and prognostic chemoresistance biomarkers.en_US
dc.identifier.urihttps://hdl.handle.net/10133/2594
dc.language.isoen_USen_US
dc.librarysymbolALU
dc.organizationUniversity of Lethbridge
dc.publisherLethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, 2010en_US
dc.publisher.departmentDepartment of Biological Sciencesen_US
dc.publisher.facultyArts and Scienceen_US
dc.relation.ispartofseriesThesis (University of Lethbridge. Faculty of Arts and Science)en_US
dc.subjectAntineoplastic agents -- Researchen_US
dc.subjectDrug resistance in cancer cells -- Researchen_US
dc.subjectEpigenetics -- Researchen_US
dc.subjectApoptosis -- Researchen_US
dc.subjectDissertations, Academicen_US
dc.titleThe role of epigenetic changes in chemoresistant breast cancer cellsen_US
dc.typeThesisen_US
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