title: Constitutive NF-kappaB activity influences basal apoptosis and radiosensitivity of head-and-neck carcinoma cell lines.
abstract: OBJECTIVE
  Nuclear factor-kappaB (NF-kappaB) has been implicated in anti-apoptotic gene transactivation, according to its transcriptional activity. The present study was designed to investigate whether constitutive NF-kappaB activity could modulate basal apoptosis and intrinsic radiosensitivity of KB head-and-neck carcinoma cell line and KB3 subline. The KB3 subline was more radiosensitive (SF2 = 0.48, alpha = 0.064) than the radioresistant KB parental cell line (SF2 = 0.80, alpha = 0.114).
  
  
  METHODS
  Constitutive NF-kappaB DNA-binding activity was determined using electrophoretic mobility shift assay. Modulation of NF-kappaB activity was performed by exposing both cell lines to tumor necrosis factor alpha or dexamethasone. Apoptotic cell population was analyzed using flow cytometry (annexin V/propidium iodide). Radiosensitivity was assessed from determination of the surviving fraction at 2 Gy (SF2), and alpha and beta parameters were determined using the linear-quadratic model.
  
  
  RESULTS
  Constitutive NF-kappaB activity was found to be significantly lower in KB3 than in KB. KB cell line exposure to dexamethasone significantly decreased NF-kappaB DNA-binding activity and, consequently, enhanced baseline apoptosis and radiosensitivity (alpha values: 0.114 vs. 0.052). Conversely, exposure of KB3 cells to tumor necrosis factor alpha increased NF-kappaB DNA-binding activity and resulted in a significant decrease (50%) in rate of apoptosis and in radiosensitivity (SF2 values: 0.48 vs. 0.63).
  
  
  CONCLUSIONS
  Modulation of NF-kappaB DNA-binding activity influences baseline apoptosis and intrinsic radiosensitivity.
authors.affiliation: Laboratoire de Recherche en Oncologie, Centre Alexis Vautrin, Nancy, France.
authors.forename: C
authors.initials: C
authors.lastname: Didelot
authors.forename: M
authors.initials: M
authors.lastname: Barberi-Heyob
authors.forename: A
authors.initials: A
authors.lastname: Bianchi
authors.forename: P
authors.initials: P
authors.lastname: Becuwe
authors.forename: J F
authors.initials: JF
authors.lastname: Mirjolet
authors.forename: M
authors.initials: M
authors.lastname: Dauça
authors.forename: J L
authors.initials: JL
authors.lastname: Merlin
mesh_terms: D017209:Apoptosis; D004247:DNA / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D016328:NF-kappa B / Q000502:physiology*; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D004247:DNA