Ayars Michael, Eshleman James, Goggins Michael
a Department of Pathology , The Johns Hopkins University School of Medicine , Baltimore , MD, USA.
b Department of Oncology , The Johns Hopkins University School of Medicine , Baltimore , MD, USA.
Cell Cycle. 2017 May 19;16(10):991-998. doi: 10.1080/15384101.2017.1312236. Epub 2017 Apr 28.
Ataxia telangiectasia mutated (ATM) is inactivated in a significant minority of pancreatic ductal adenocarcinomas and may be predictor of treatment response. We determined if ATM deficiency renders pancreatic cancer cells more sensitive to fractionated radiation or commonly used chemotherapeutics. ATM expression was knocked down in three pancreatic cancer cell lines using ATM-targeting shRNA. Isogenic cell lines were tested for sensitivity to several chemotherapeutic agents and radiation. DNA repair kinetics were analyzed in irradiated cells using the comet assay. We find that while rendering pancreatic cancer cells ATM-deficient did not significantly change their sensitivity to several chemotherapeutics, it did render them exquisitely sensitized to radiation. Pancreatic cancer ATM status may help predict response to radiotherapy.
共济失调毛细血管扩张症突变基因（ATM）在相当一部分胰腺导管腺癌中失活，可能是治疗反应的预测指标。我们研究了ATM缺陷是否会使胰腺癌细胞对分次放疗或常用化疗药物更敏感。使用靶向ATM的短发夹RNA（shRNA）在三种胰腺癌细胞系中敲低ATM表达。对同基因细胞系进行了几种化疗药物和放疗的敏感性测试。使用彗星试验分析受辐照细胞的DNA修复动力学。我们发现，虽然使胰腺癌细胞缺乏ATM不会显著改变它们对几种化疗药物的敏感性，但确实使它们对放疗极为敏感。胰腺癌的ATM状态可能有助于预测放疗反应。
