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doi:10.11889/j.1000-3436.2015.rrj.33.020203

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更新时间：2021-12-01

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- Journal of Radiation Research and Radiation Processing Vol. 33, Issue 2, Pages: 20203-020203(2015)
- 作者机构：
  
  1. 1（复旦大学放射医学研究所）,上海,200032
  2. 2（淮安市妇幼保健院儿童保健科）,淮安,223002
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- DOI：10.11889/j.1000-3436.2015.rrj.33.020203
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[J]. Journal of Radiation Research and Radiation Processing 33(2):20203-020203(2015)
DOI：

[J]. Journal of Radiation Research and Radiation Processing 33(2):20203-020203(2015) DOI： 10.11889/j.1000-3436.2015.rrj.33.020203.

摘要

实验以具有不同卵巢癌差异表达基因2相互作用蛋白(Disabled homolog 2 interaction protein, DAB2IP)表达的前列腺癌细胞为研究对象，讨论DNA损伤修复关键蛋白-共济失调毛细血管扩张症基因突变(Ataxia-telangiectasia mutated, ATM)在DAB2IP影响肿瘤细胞放射敏感性中的作用。研究比较了单纯γ-射线(0、2、4、6、8 Gy)和ATM特异性抑制剂-KU55933(10 μmol/L)联合射线作用后，不同DAB2IP表达的前列腺癌细胞集落形成率的差异；采用qRT-PCR及Western blot方法分别检测了2 Gy和KU55933+2 Gy照射后，细胞内ATM在翻译转录、蛋白表达和磷酸化水平的变化。结果显示，同一吸收剂量下，DAB2IP基因沉默的前列腺癌细胞，集落形成能力明显高于DAB2IP阳性表达的对照组细胞，并伴随着ATM合成与磷酸化水平的升高。KU55933通过抑制ATM 的翻译转录与蛋白磷酸化，可显著增强射线对低表达DAB2IP的辐射耐受细胞的损伤作用。提示ATM是DAB2IP基因沉默引起肿瘤细胞辐射耐受的关键分子，可以ATM为靶点筛选药物，提高DAB2IP基因缺陷的肿瘤患者对放射治疗的敏感性。

Abstract

The role of ATM in radio-resistant PCa cells caused by DAB2IP knockdown was investigated in this study. The response of two PCa cell lines, PC3 shVector and PC3 shDAB2IP to γ-rays (0, 2, 4, 6, 8 Gy) alone or combined with 10 μmol/L KU55933, an ATM inhibitor, were measured by a colony formation assay. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot were used to determine the amount of ATM mRNA and ATM phosphorylation, respectively. The results showed that DAB2IP-knockdown cells (PC3 shDAB2IP) exhibited increased clonogenic survival in response to IR compared with control cells (PC3 shVector) expressing an endogenous level of DAB2IP. KU55933 significantly sensitized PC3 shDAB2IP cells to IR due to inhibition the ATM mRNA synthesis and ATM phosphorylation. It suggests that elevated ATM expression and activation observed in DAB2IP deficient cells could be a key event in resulting in resistance to IR, and ATM inhibitor could be applied to improve the radio-sensitivity of PCa patients with DAB2IP genetic defects.Cited

关键词

前列腺癌辐射敏感性卵巢癌差异表达基因2相互作用蛋白共济失调毛细血管扩张症基因突变

Keywords

Prostate cancerRadio-sensitivityDisabled homolog 2 interaction proteinAtaxia-telangiectasia mutated

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DOI：10.11889/j.1000-3436.2015.rrj.33.020203

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