This thesis reports that checkpoint adaptation occurs in human brain cancer cells. M059K cells, after treatment with camptothecin (CPT), recruited γ-histone H2AX, phosphorylated Chk1 and arrested in the G2 phase. Strikingly, cells escaped the checkpoint, became rounded and entered mitosis as measured by phospho-histone H3 signals. Lamin A/C immunofluorescence microscopy revealed that 48% of the cells that survived checkpoint adaptation contained micronuclei. These data suggest that brain cancer cells undergo checkpoint adaptation and may have an altered genome. This thesis also explored if phosphatases participate in checkpoint adaptation. Human colon cancer cells were treated with CPT and the PP2A inhibitor cantharidin. Following treatment the cells became rounded and 65% were positive for phospho-histone H3 signals indicating that cantharidin caused cells to be in mitosis following CPT treatment. These data suggest that PP2A might have a role in checkpoint adaptation, or participate in a pathway that bypasses checkpoint adaptation. / xi, 114 leaves : ill. (some col.) ; 29 cm
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:ALU.w.uleth.ca/dspace#10133/3390 |
| Date | January 2012 |
| Creators | Lanser, Brittany |
| Contributors | Golsteyn, Roy |
| Publisher | Lethbridge, Alta. : University of Lethbridge, Dept. of Biological Sciences, c2012, Arts and Science, Department of Biological Sciences |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | en_CA |
| Detected Language | English |
| Type | Thesis |
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