The roles of MLH1 and MSH2 in growth and drug resistance in human colorectal cancer cells

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The roles of MLH1 and MSH2 in growth and drug resistance in human colorectal cancer cells

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dc.contributor.advisor Coomber, Brenda
dc.contributor.author Barber, Amanda
dc.date 2012-08-29
dc.date.accessioned 2012-09-06T19:33:22Z
dc.date.available 2012-09-06T19:33:22Z
dc.date.issued 2012-09-06
dc.identifier.uri http://hdl.handle.net/10214/3939
dc.description.abstract Loss of genomic stability is associated with a variety of diseases, particularly cancer. Of the many proteins which maintain genomic integrity, two of the most important are MLH1 and MSH2, which participate in DNA mismatch repair. Previous work established derivatives of the CaCo2 human colorectal cancer cell line with siRNA-mediated knockdown of these proteins. When xenografted into mice, tumors with reduced MLH1 or MSH2 expression grew faster than controls. Following growth in vivo, clonal cell lines were established from the tumors and used to examine the effects that knockdown of MSH2 had on other members of the DNA mismatch repair system. Clonal survival following exposure to 5-fluorouracil was also evaluated, and those cells with reduced MLH1 and MSH2 levels were found to be resistant. This study has implications for the importance of knowing the MMR status of a given tumor when deciding on a course of treatment, and of the compounding effects of the loss of one MMR protein on others in the family. en_US
dc.description.sponsorship Canadian Cancer Society Research Institute en_US
dc.language.iso en en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.5/ca/ *
dc.subject DNA Repair en_US
dc.subject Colorectal cancer en_US
dc.subject Mismatch repair en_US
dc.subject Drug resistance en_US
dc.title The roles of MLH1 and MSH2 in growth and drug resistance in human colorectal cancer cells en_US
dc.type Thesis en_US
dc.degree.programme Biomedical Sciences en_US
dc.degree.name Master of Science en_US
dc.degree.department Department of Biomedical Sciences en_US


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http://creativecommons.org/licenses/by/2.5/ca/ Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/2.5/ca/

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