Methylenetetrahydrofolate reductase (MTHFR) is an important enzyme in the metabolism of folate and methionine. MTHFR catalyzes the conversion of 5,10 methylenetetrahydrofolate (5,10-methyleneTHF) to 5-methyltetrahydrofolate (5-methylTHF). 5-MethylTHF is a co-substrate for homocysteine remethylation to methionine catalyzed by the vitamin B12-dependent enzyme methionine synthase. A common MTHFR variant, 677C → T substitution resulting in the conversion of an alanine to a valine residue, has been shown to be a thermolabile form of MTHFR and to have reduced activity (Frosst et al., 1995). Since many diverse cancer cells have been documented to be methionine-dependent in culture, the effects of MTHFR downregulation on cell survival of transformed cells was examined. In addition, the influence of the MTHFR 677C → T polymorphism on the sensitivity of transformed lines to antifolate drug treatment was studied. / To test the effect of decreased MTHFR expression on cell viability, we transfected antisense oligonucleotides (ASOs) complementary to the MTHFR mRNA into the colon carcinoma cell line SW620. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.33029 |
| Date | January 2001 |
| Creators | Sekhon, Jaspreet. |
| Contributors | Rozen, Rima (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Human Genetics.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001838168, proquestno: MQ75343, Theses scanned by UMI/ProQuest. |
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