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dc.contributor.supervisor Kovalchuk, Olga
dc.contributor.author Filkowski, Jody
dc.contributor.author University of Lethbridge. Faculty of Arts and Science
dc.date.accessioned 2012-01-31T18:13:52Z
dc.date.available 2012-01-31T18:13:52Z
dc.date.issued 2010
dc.identifier.uri https://hdl.handle.net/10133/2594
dc.description xiii, 116 leaves : ill. (some col.) ; 29 cm en_US
dc.description.abstract Cytotoxic 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.language.iso en_US en_US
dc.publisher Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, 2010 en_US
dc.relation.ispartofseries Thesis (University of Lethbridge. Faculty of Arts and Science) en_US
dc.subject Antineoplastic agents -- Research en_US
dc.subject Drug resistance in cancer cells -- Research en_US
dc.subject Epigenetics -- Research en_US
dc.subject Apoptosis -- Research en_US
dc.subject Dissertations, Academic en_US
dc.title The role of epigenetic changes in chemoresistant breast cancer cells en_US
dc.type Thesis en_US
dc.publisher.faculty Arts and Science en_US
dc.publisher.department Department of Biological Sciences en_US
dc.degree.level Doctor of Philosophy
dc.degree.discipline Biological Sciences
dc.organization University of Lethbridge
dc.librarysymbol ALU
dc.degree.field Arts and Sciences
dc.degree.subfield Sciences


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