ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts.
The heritable disorder ataxia telangiectasia (AT) is caused by mutations in the AT-mutated (ATM) gene with manifestations that include predisposition to lymphoproliferative cancers and hypersensitivity to ionizing radiation (IR). We investigated gene expression changes in response to IR in human lymphoblasts and fibroblasts from seven normal and seven AT-affected individuals. Both cell types displayed ATM-dependent gene expression changes after IR, with some responses shared and some responses varying with cell type and dose. Interestingly, after 5 Gy IR, lymphoblasts displayed ATM-independent responses not seen in the fibroblasts at this dose, which likely reflect signaling through ATM-related kinases, e.g., ATR, in the absence of ATM function.
Innes
Cynthia L
CL
Growth Control and Cancer Group, National Institute of Environmental Health Sciences, PO Box 12233, MD D2-03, Research Triangle Park, NC 27709, USA.
Heinloth
Alexandra N
AN
Flores
Kristina G
KG
Sieber
Stella O
SO
Deming
Paula B
PB
Bushel
Pierre R
PR
Kaufmann
William K
WK
Paules
Richard S
RS
D001260:Ataxia Telangiectasia / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D016193:G1 Phase / Q000235:genetics / Q000528:radiation effects; D016195:G2 Phase / Q000235:genetics / Q000528:radiation effects; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases