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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 Barber, Amanda 2012-08-29 2012-09-06T19:33:22Z 2012-09-06T19:33:22Z 2012-09-06
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 *
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 Biomedical Sciences en_US Master of Science en_US Department of Biomedical Sciences en_US

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