Objetivo Cellular senescence was originally described as the cell cycle arrest that accompanies the exhaustion of replicative potential in cultured primary mammalian cells. Whereas ‘replicative’ senescence is triggered by telomere erosion, other stimuli such as activated oncogenes, oxidative stress, DNA damage and sub-optimal culture conditions can also induce a senescent phenotype called ‘premature’ senescence or ‘stasis’. Senescence acts as a potent antitumor mechanism. Malignant transformation occurs after the bypass of senescence caused by mutations in oncogenes and tumour suppressors. Thus, novel genes linked with oncogenesis can be isolated by identifying genes regulating senescence. As the majority of solid tumours arise from cells of epithelial origin, the aim of the current project is to identify genes controlling senescence in epithelial cells. Specifically, human prostate epithelial cells (HprECs) will be studied as the corresponding prostate cancer represents the most frequent cancer amongst men. A genetic screening for senescence bypass will be performed in these cells using a retroviral shRNA library. The validated genes will be prioritized thanks to a parallel microarray based-analysis of transcriptional changes associated with senescence in HPrECs and to existing databases that evaluate expression profiles in human tumours. The expression of the relevant candidates will be then confirmed in a wider and independent subset of clinical tumour samples using tissue micro-array. Finally, the oncogenic properties of the candidate genes will be analysed in several models of tumourigenesis. Overall, the investigation described here aims at using senescence as a system to identify novel tumour suppressor genes. Ámbito científico medical and health sciencesclinical medicineoncologyprostate cancernatural sciencescomputer and information sciencesdatabasesnatural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological sciencesgeneticsmutation Programa(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Tema(s) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Convocatoria de propuestas FP7-PEOPLE-2009-IEF Consulte otros proyectos de esta convocatoria Régimen de financiación MC-IEF - Intra-European Fellowships (IEF) Coordinador IMPERIAL COLLEGE OF SCIENCE TECHNOLOGY AND MEDICINE Aportación de la UE € 171 740,80 Dirección SOUTH KENSINGTON CAMPUS EXHIBITION ROAD SW7 2AZ LONDON Reino Unido Ver en el mapa Región London Inner London — West Westminster Tipo de actividad Higher or Secondary Education Establishments Contacto administrativo Palalic Tatjana (Ms.) Enlaces Contactar con la organización Opens in new window Sitio web Opens in new window Coste total Sin datos