Cancer has been thought of as a mostly genetic phenomenon, however recent research into epigenetic causes of cancer emphasizes that these causes of cancer are also important. RIZ1 is a tumor suppressor which is silenced in many human leukemias, such as human Acute Myeloid Leukemia and Chronic Myelogenous Leukemia. It was the goal of this thesis to re-express RIZ1 using three epigenetic drugs: decitabine, a DNA methylation inhibitor, Trichostatin A, a histone deacetylase inhibitor and chaetocin, an inhibitor of SUV39h1. Cells were treated with these drugs and analyzed for toxicity, methylation status, and RIZ1 expression levels. The synergy between the drugs was also determined. It was found that cells treated with decitabine and chaetocin had an induction of RIZ1 expression. Chaetocin induced RIZ1 expression without affecting the methylation status of the cell. Also, cells which were treated with decitabine paired with either Trichostatin A or chaetocin showed the highest amount of RIZ1 expression. Cells treated with all three drugs together had a higher amount of RIZ1 expression than cells treated with either drug alone, however had less expression than cells which had been treated with decitabine paired with either Trichostatin A or chaetocin. Using these data a model was developed in which H3K9 methylation is the dominant epigenetic event in transcriptional silencing.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:SSU.etd-12222008-150903 |
| Date | 05 January 2009 |
| Creators | Beaton-Brown, Erika Lauren Dawn |
| Contributors | Nazarali, Adil J., Laferte, Suzanne, Khandelwal, Ramji L., Geyer, C. Ronald, Roesler, William J. |
| Publisher | University of Saskatchewan |
| 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 | text |
| Format | application/pdf |
| Source | http://library.usask.ca/theses/available/etd-12222008-150903/ |
| Rights | unrestricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to University of Saskatchewan or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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