NFκB and survivin-mediated radio-adaptive response

David J. Grdina, Jeffrey S. Murley, Richard C. Miller, Gayle E. Woloschak, Jian-Jian Li

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)391-397
Number of pages7
JournalRadiation Research
Volume183
Issue number4
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Biophysics
  • Radiation
  • Medicine(all)

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  • Cite this

    Grdina, D. J., Murley, J. S., Miller, R. C., Woloschak, G. E., & Li, J-J. (2015). NFκB and survivin-mediated radio-adaptive response. Radiation Research, 183(4), 391-397. https://doi.org/10.1667/RR14002.1