Senescence signaling, regulation and bypass by telomere maintenance

RC0254 Neoplasms. Tumors. Oncology (including Cancer)

Lafferty-Whyte, Kyle ; Keith, W. Nicol

University:University of Glasgow

Department:Institute of Cancer Sciences

关键词: senescence, immortalisation, telomere maintenance, mesenchymal, stem cells, c-Myc, TCEAL7, gene expression, microRNA, pathway analysis, latent signaling scoring;   

Others  :  http://theses.gla.ac.uk/2212/1/2010Lafferty-WhitePhd.pdf

来源: University of Glasgow

【 摘 要 】

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.