Lack of involvement of ataxia telangiectasia mutated (ATM) in regulation of nuclear factor-kappaB (NF-kappaB) in human diploid fibroblasts.
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.
Ashburner
B P
BP
Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill 27599, USA.
Shackelford
R E
RE
Baldwin
A S
AS
Paules
R S
RS
D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D002467:Cell Nucleus / Q000378:metabolism / Q000528:radiation effects; D019926:Cyclin B / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism / Q000528:radiation effects; D004268:DNA-Binding Proteins; D005347:Fibroblasts / Q000378:metabolism* / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006657:Histones / Q000378:metabolism; D006801:Humans; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011839:Radiation, Ionizing; D013997:Time Factors; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D019926:Cyclin B; D004268:DNA-Binding Proteins; D006657:Histones; D016328:NF-kappa B; D011506:Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases