title: Absence of p21WAF1 cooperates with c-myc in bypassing Ras-induced senescence and enhances oncogenic cooperation.
abstract: The absence of p21waf1 combined with an ectopic expression of c-myc prevents ras-induced senescence in mouse embryo fibroblasts. Extension of lifespan after c-myc transduction into p21-null cells was followed at later passages by apoptosis of a large fraction of c-myc-overexpressing p21-null cells. This apoptotic effect could be overridden by inactivation of the p53 tumor suppressor or oncogenic ras expression. Ras-induced inhibition of apoptosis is mediated by PI3K activation. These results suggest a functional relationship between ras and myc that may explain their oncogenic cooperation. The number of foci formed by myc+ras increased cooperatively in the absence of p21waf1. Thus, the reciprocal cooperation between myc and ras in a p21-null background during cellular immortalization lead to increased oncogenic cooperation between ras and myc.
authors.affiliation: Experimental Therapeutics Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain. acarnero@cnio.es
authors.forename: Amancio
authors.initials: A
authors.lastname: Carnero
authors.forename: David H
authors.initials: DH
authors.lastname: Beach
mesh_terms: D000818:Animals; D016922:Cellular Senescence; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000502:physiology*; D016259:Genes, myc / Q000502:physiology*; D011905:Genes, ras / Q000502:physiology*; D051379:Mice; D009369:Neoplasms / Q000209:etiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology
chemical_list: C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D019869:Phosphatidylinositol 3-Kinases