ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts

Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, North Carolina, United States
Molecular Cancer Research (Impact Factor: 4.5). 04/2006; 4(3):197-207. DOI: 10.1158/1541-7786.MCR-05-0154
Source: PubMed

ABSTRACT 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.

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