title: Requirement of NF-kappaB activation to suppress p53-independent apoptosis induced by oncogenic Ras.
abstract: The ras proto-oncogene is frequently mutated in human tumors and functions to chronically stimulate signal transduction cascades resulting in the synthesis or activation of specific transcription factors, including Ets, c-Myc, c-Jun, and nuclear factor kappa B (NF-kappaB). These Ras-responsive transcription factors are required for transformation, but the mechanisms by which these proteins facilitate oncogenesis have not been fully established. Oncogenic Ras was shown to initiate a p53-independent apoptotic response that was suppressed through the activation of NF-kappaB. These results provide an explanation for the requirement of NF-kappaB for Ras-mediated oncogenesis and provide evidence that Ras-transformed cells are susceptible to apoptosis even if they do not express the p53 tumor-suppressor gene product.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: M W
authors.initials: MW
authors.lastname: Mayo
authors.forename: C Y
authors.initials: CY
authors.lastname: Wang
authors.forename: P C
authors.initials: PC
authors.lastname: Cogswell
authors.forename: K S
authors.initials: KS
authors.lastname: Rogers-Graham
authors.forename: S W
authors.initials: SW
authors.lastname: Lowe
authors.forename: C J
authors.initials: CJ
authors.lastname: Der
authors.forename: A S
authors.initials: AS
authors.lastname: Baldwin
mesh_terms: D016475:3T3 Cells; D017500:Adenovirus E1A Proteins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D002461:Cell Line, Transformed; D002470:Cell Survival; D002471:Cell Transformation, Neoplastic; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D011905:Genes, ras; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051381:Rats; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000502:physiology
chemical_list: D017500:Adenovirus E1A Proteins; C000715470:MAS1 protein, human; D016328:NF-kappa B; D000090063:Proto-Oncogene Mas; D016159:Tumor Suppressor Protein p53