Faculty of Science
School of Molecular Medicine and Haematology
Masters Dissertation / Studies on the development of drug resistance in several cancer types, including acute myeloid leukaemia (AML), have implicated the PI3-kinase pathway. This pathway phosphorylates Akt resulting in the activation of proteins involved in cell survival. The aim of this study is to determine the role that Akt plays in urvival and the relationship between Akt, IKK and IkB in HL-60 cells. This study demonstrated that etoposide caused apoptosis in HL-60 cells, which was slightly increased when the PI3-kinase pathway was inhibited by LY294002. Stimulation with PDGF resulted in cell proliferation and increased Akt, IKK and IkB
phosphorylation. Although pre-treatment with LY294002 decreased the amount of Phospho-Akt, phosphorylation of IKK and IkB still occurred.
Therefore additional pathways must be involved in IkB regulation in HL-60 cells. Akt mRNA transcription was decreased when the cells were pretreated with LY294002 and either PDGF or etoposide. In conclusion, the
PI3-kinase pathway plays a minor role in the survival of HL-60 cells and Akt substrates other than IKK are mediating this survival.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:wits/oai:wiredspace.wits.ac.za:10539/1444 |
| Date | 25 October 2006 |
| Creators | Drummond, Chantal, Paula |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Format | 7517620 bytes, application/pdf, application/pdf |
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