Lack of involvement of ataxia telangiectasia mutated (ATM) in regulation of nuclear factor-kappaB (NF-kappaB) in human diploid fibroblasts

Cancer Res. 1999 Nov 1;59(21):5456-60.

Abstract

It has been suggested that the cellular response to exposure to ionizing radiation involves activation of the transcription factor nuclear factor-kappaB (NF-kappaB) and that this response is defective in cells from individuals with ataxia telangiectasia (AT). In one study, it was found that SV40 large T-transformed cells derived from a patient null for the AT mutated (ATM) gene exhibited constitutive activation of NF-kappaB and that in those cells, inhibition of NF-kappaB by expression of a modified form of IkappaBalpha led to correction of the radiosensitivity associated with the AT phenotype [M. Jung et al., Science (Washington DC), 268: 1691-1621, 1995]. From those data, it was suggested that NF-kappaB played a role in the AT phenotype. We show here that normal diploid cells derived from AT patients do not exhibit constitutive activation of NF-kappaB. Furthermore, we provide data that the transformation process associated with SV40 large T antigen expression in AT-/- cells leads to aberrant cellular responses. Our studies highlight the importance of using diploid, nontransformed AT-/- cells for in vitro studies relevant to the AT phenotype whenever possible.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Ataxia Telangiectasia / genetics
  • Ataxia Telangiectasia Mutated Proteins
  • Cell Cycle Proteins
  • Cell Nucleus / metabolism
  • Cell Nucleus / radiation effects
  • Cyclin B / metabolism
  • Cytoplasm / metabolism
  • Cytoplasm / radiation effects
  • DNA-Binding Proteins
  • Fibroblasts / metabolism*
  • Fibroblasts / radiation effects
  • Gene Expression Regulation, Neoplastic*
  • Histones / metabolism
  • Humans
  • NF-kappa B / genetics*
  • NF-kappa B / metabolism*
  • Protein Serine-Threonine Kinases*
  • Proteins / genetics*
  • Proteins / metabolism
  • RNA, Messenger / metabolism
  • Radiation, Ionizing
  • Time Factors
  • Tumor Suppressor Proteins

Substances

  • Cell Cycle Proteins
  • Cyclin B
  • DNA-Binding Proteins
  • Histones
  • NF-kappa B
  • Proteins
  • RNA, Messenger
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein Serine-Threonine Kinases