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dc.contributor.advisorLukong, Kivenen_US
dc.creatorDai, Chenluen_US
dc.date.accessioned2015-01-30T12:00:10Z
dc.date.available2015-01-30T12:00:10Z
dc.date.created2015-01en_US
dc.date.issued2015-01-29en_US
dc.date.submittedJanuary 2015en_US
dc.identifier.urihttp://hdl.handle.net/10388/ETD-2015-01-1922en_US
dc.description.abstractThe human Fyn-related kinase (FRK) is a member of subfamily of Src-related kinases family. FRK is 54 kDa non-receptor tyrosine kinase protein composed of 505 amino acids. FRK consists of three functional domains: Src homology 3 (SH3), SH2 and kinase domain, as well as a putative tyrosine kinase regulator at the C-terminus. FRK has a conserved auto-regulatory tyrosine residue within its kinase domain. It has been reported that FRK is repressed in about 30 % of human breast cancer samples. Over-expression of FRK in breast cancer cells of the mammary gland was shown to suppress cell growth by interacting, phosphorylating and stabilizing the tumor suppressor PTEN, thus inhibiting AKT/PI3K signaling. Although it has been suggested that FRK is a tumor suppressor gene, the effects of activated FRK on cell proliferation, migration and invasion are unclear. Likewise, the signaling pathways regulated by the activation of FRK have not been yet fully characterized. We hypothesize that the activation of FRK is essential for the regulation of its cellular functions. Mutation of the C-terminal auto-regulatory tyrosine 497 to phenylalanine (FRK-Y497F) resulted in the constitutive activation of FRK. We generated stable cell lines expressing either the FRK wild type (FRK-WT) or FRK-Y497F from triple negative breast cancer MDA-MB-231 cells. The introduction of FRK-Y497F in MDA-MB-231 cells significantly suppressed their proliferation, migration, invasiveness and colony formation as compared to cells that expressed the FRK-WT gene. Over-expression of either FRK-WT or FRK-Y497F in MDA-MB-231 cells inhibited the phosphorylation of AKT, STAT3, JNK and P38 MAPK as compared to either the MDA-MB-231 parental cells or those that were transfected with the empty vector. Our results suggested that FRK represses cell proliferation, migration, invasiveness and colony formation at least in part by the inhibiting the activation of AKT/PI3K, JAK-STAT and MAPK signaling pathways.en_US
dc.language.isoengen_US
dc.subjectFRKen_US
dc.subjectbreast canceren_US
dc.subjectSTAT3en_US
dc.titleEffects of Fyn-related kinase activity on breast cancer cell proliferation, migration, invasion and colony formationen_US
thesis.degree.departmentBiochemistryen_US
thesis.degree.disciplineBiochemistryen_US
thesis.degree.grantorUniversity of Saskatchewanen_US
thesis.degree.levelMastersen_US
thesis.degree.nameMaster of Science (M.Sc.)en_US
dc.type.materialtexten_US
dc.type.genreThesisen_US
dc.contributor.committeeMemberChelico, Lindaen_US
dc.contributor.committeeMemberStone, Scoten_US
dc.contributor.committeeMemberBonham, Keithen_US


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