Innes Cynthia L, Heinloth Alexandra N, Flores Kristina G, Sieber Stella O, Deming Paula B, Bushel Pierre R, Kaufmann William K, Paules Richard S
Growth Control and Cancer Group, National Institute of Environmental Health Sciences, PO Box 12233, MD D2-03, Research Triangle Park, NC 27709, USA.
Mol Cancer Res. 2006 Mar;4(3):197-207. doi: 10.1158/1541-7786.MCR-05-0154.
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.
遗传性疾病共济失调毛细血管扩张症（AT）由AT突变（ATM）基因的突变引起，其表现包括易患淋巴增殖性癌症和对电离辐射（IR）敏感。我们研究了来自7名正常人和7名AT患者的人类淋巴母细胞和成纤维细胞对IR的基因表达变化。两种细胞类型在IR后均显示出依赖ATM的基因表达变化，一些反应是共同的，而一些反应则因细胞类型和剂量而异。有趣的是，在5 Gy IR后，淋巴母细胞显示出在该剂量下成纤维细胞中未见的不依赖ATM的反应，这可能反映了在缺乏ATM功能的情况下通过ATM相关激酶（例如ATR）的信号传导。
