Neuhäuser Katharina, Küper Leonie, Christiansen Hans, Bogdanova Natalia
Radiation Oncology Research Unit, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
Gynaecology Research Unit, Hannover Medical School, Carl-Neuberg Str. 1, 30625 Hannover, Germany.
Clin Transl Radiat Oncol. 2019 Jan 24;15:99-107. doi: 10.1016/j.ctro.2019.01.006. eCollection 2019 Feb.
The translationally controlled tumor protein 1 (TPT1/TCTP) has been implicated in the intracellular DNA damage response. We tested the role of TPT1 in breast cancer (BC) predisposition and re-evaluated its function in Ataxia-Telangiectasia mutated (ATM)-mediated damage recognition and DNA repair.
The coding sequence was scanned for mutations in genomic DNA from 200 breast cancer patients. was down-regulated through siRNA in breast epithelial and fibroblast cell cultures. ATM activation after irradiation (IR) was analyzed by western blotting, and γH2A.X foci were monitored by immunocytochemistry.
The sequencing study identified a novel, potentially damaging missense mutation in a single patient. Silencing of did not significantly affect ATM kinase activity and did not impair the initial formation of γH2A.X foci, while we observed a marginally significant effect on residual γH2A.X foci at 6-48 h after IR.
does not harbor common mutations as BC susceptibility gene. Consistently, TPT1 protein is not required for the recognition of radiation-induced DNA damage via the ATM-dependent pathway and has only slight impact on timely repair. These results may be important when considering TPT1 as a DNA damage marker.
翻译控制肿瘤蛋白1（TPT1/TCTP）与细胞内DNA损伤反应有关。我们测试了TPT1在乳腺癌（BC）易感性中的作用，并重新评估了其在共济失调毛细血管扩张症突变（ATM）介导的损伤识别和DNA修复中的功能。
对200例乳腺癌患者的基因组DNA编码序列进行突变扫描。通过siRNA在乳腺上皮和成纤维细胞培养物中下调TPT1。通过蛋白质印迹分析照射（IR）后ATM的激活情况，并通过免疫细胞化学监测γH2A.X焦点。
测序研究在一名患者中发现了一种新的、可能具有破坏性的错义突变。TPT1的沉默并未显著影响ATM激酶活性，也未损害γH2A.X焦点的初始形成，而我们在IR后6-48小时观察到对残留γH2A.X焦点有轻微显著影响。
TPT1并非作为BC易感基因存在常见突变。一致地，通过ATM依赖性途径识别辐射诱导的DNA损伤不需要TPT1蛋白，且对及时修复仅有轻微影响。在将TPT1视为DNA损伤标志物时，这些结果可能很重要。
