title: NFκB and Survivin-Mediated Radio-Adaptive Response.
abstract: A survivin-mediated radio-adaptive response was induced in SA-NH murine sarcoma cells following activation of nuclear transcription factor κB (NFκB) by very low doses of ionizing radiation of 5, 20 or 100 mGy. SA-NH cells and a clone stably transfected with a plasmid containing a mutated IκBα gene that prevents the activation of NFκB (SA-NH+mIκBα1) were used to investigate the role of NFκB activation in the development and expression of the survivin-mediated radio-adaptive response. Tumor cells were exposed to very low doses of radiation 30 min prior to or at times ranging from 30 min to 6 h after the first of two 2 Gy doses separated by 24 h under in vitro conditions. Evidence of very low dose radiation induced a radio-adaptive response only in SA-NH but not SA-NH+mIκBα1 cells was shown by both an increase in SA-NH cell survival of 20-40% using a standard colony forming assay and reduced apoptosis frequencies of 20-40% as determined by the TUNEL assay. Changes in survivin protein levels as a function of irradiation conditions were monitored by Western blot. A 100 mGy exposure 30 min prior to a 2 Gy dose resulted in an elevation in total survivin protein 24 h later in SA-NH but not SA-NH+mIκBα1 cells. Transfection of cells with survivin siRNA inhibited elevation of survivin protein by very low dose radiation and the subsequent radio-adaptive response in SA-NH cells. These data suggest that the survivin-mediated radio-adaptive response is dependent upon the ability of cells to activate NFκB.
authors.affiliation: a  Department of Radiation and Cellular Oncology, The University of Chicago, Chicago, Illinois 60637;
authors.forename: David J
authors.initials: DJ
authors.lastname: Grdina
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Murley
authors.forename: Richard C
authors.initials: RC
authors.lastname: Miller
authors.forename: Gayle E
authors.initials: GE
authors.lastname: Woloschak
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
mesh_terms: D000222:Adaptation, Physiological / Q000528:radiation effects*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism*; D000077022:Survivin
chemical_list: C117749:Birc5 protein, mouse; D051034:Inhibitor of Apoptosis Proteins; D016328:NF-kappa B; D012097:Repressor Proteins; D000077022:Survivin