Senescence signaling, regulation and bypass by telomere maintenance

Lafferty-Whyte, Kyle (2010) Senescence signaling, regulation and bypass by telomere maintenance. PhD thesis, University of Glasgow.

Abstract

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.

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Additional Information: Chapter 3 published in 2 parts in Oncogene and Neoplasia journals. Sections of Chapter 4 published in Biochimica et Biophysica Acta. Chapter 5 published in BMC Genomics.
• Keywords: senescence, immortalisation, telomere maintenance, mesenchymal, stem cells, c-Myc, TCEAL7, gene expression, microRNA, pathway analysis, latent signaling scoring
• Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
• Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Supervisor's Name: Keith, Prof. W. Nicol
• Date of Award: 2010
• Depositing User: Mr Kyle Lafferty-Whyte
• Unique ID: glathesis:2010-2212
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 11 Aug 2011
• Last Modified: 11 Aug 2014 08:15
• URI: https://theses.gla.ac.uk/id/eprint/2212