The permanent cell cycle arrest known as cellular senescence is a major block to tumorigenesis. Currently the effects of latent senescence signaling on disease progression, response to therapy and outcome are poorly understood. Furthermore, the role of microRNAs in the regulation of senescence remains to be fully elucidated. For immortalisation to occur replicative senescence must be bypassed usually by activating a telomere maintenance mechanism (TMM). However, the expression differences between TMMs are also poorly understood. To address these questions a combination of gene expression and miRNA microarray profiling, virtual drug and siRNA kinase screening were utilised. These findings highlight the distinct roles of secretory and damage associated senescence pathways in disease progression and in response to therapy. Examination of the differentially expressed genes between TMMs also highlighted a differentially expressed gene expression network surrounding TERT, regulated by c-Myc and TCEAL7 in TMMs. These findings give further insight into the complex regulation network surrounding senescence signaling during tumorigenesis.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:523345 |
| Date | January 2010 |
| Creators | Lafferty-Whyte, Kyle |
| Publisher | University of Glasgow |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://theses.gla.ac.uk/2212/ |
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