The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer
The association of DNA-dependent protein kinase activity with chromosomal instability and risk of cancer
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DOI：
10.1093/carcin/bgi175
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发表时间：
2006-01-01
期刊：
影响因子：
4.7
通讯作者：
Hareyama, M
中科院分区：
文献类型：
--
作者：
Someya, M;Sakata, K;Hareyama, M
DNA 双链断裂 (DSB) 修复途径通过抑制染色体重排来维持基因组完整性。 DNA 依赖性蛋白激酶 (DNA-PK) 在 DNA DSB 修复中发挥重要作用。在这项研究中，招募了 93 名未经治疗的癌症患者和 41 名未患癌症的健康志愿者。采集外周血，分离、离心； DNA-PK 活性通过 DNA-pull-down 测定来测量。通过RT-PCR检测和蛋白质印迹法检测DNA-PKcs、Ku70和Ku86的表达。通过细胞遗传学方法检查染色体畸变。宫颈癌或乳腺癌患者外周血淋巴细胞（PBL）DNA-PK活性显着低于正常志愿者。年龄和吸烟与DNA-PK活性无关，而DNA-PK活性与RT-PCR中Ku70、Ku86和DNA-PKcs的表达相关。在蛋白质印迹测定中也看到了类似的趋势，但不如 RT-PCR 清楚。因此，无法得出DNA-PK活性与蛋白质水平上DNA-PK表达之间的关联。随着DNA-PK活性的降低，双着丝粒染色体和过量片段等染色体畸变的频率增加。总之，DNA-PK 活性与染色体不稳定有关。 PBL 中的 DNA-PK 活性与乳腺癌和宫颈癌的风险相关。 PBL 中的 DNA-PK 活性可用于选择应进行检查的个体，因为他们对乳腺癌和宫颈癌的易感性增加。
The DNA double-strand breaks (DSBs) repair pathway has been implicated in maintaining genomic integrity via suppression of chromosomal rearrangements. DNA-dependent protein kinase (DNA-PK) has an important role with DNA DSBs repair. In this study, 93 of untreated cancer patients and 41 of cancer-free healthy volunteers were enrolled. Peripheral blood was collected, separated and centrifuged; DNA-PK activity was measured by DNA-pull-down assay. The expressions of DNA-PKcs, Ku70 and Ku86 were examined by RT-PCR assay and western blotting. Chromosomal aberrations were examined by cytogenetic methods. DNA-PK activities of peripheral blood lymphocytes (PBL) in patients with uterine cervix or breast cancer were significantly lower than those in normal volunteers. Age and smoking had no association with DNA-PK activity, whereas DNA-PK activity and the expression of Ku70, Ku86 and DNA-PKcs in RT-PCR were interrelated. A similar tendency was seen in western blot assay but less clear than in RT-PCR. Therefore, the association between DNA-PK activity and expression of DNA-PK in protein level could not be concluded. The frequency of chromosome aberration, such as dicentric chromosomes and excess fragment increased as the DNA-PK activity decreased. In conclusion, DNA-PK activity is associated with chromosomal instability. DNA-PK activity in PBL is associated with risk of breast and uterine cervix cancer. DNA-PK activity in PBL can be used to select individuals for whom an examination should be performed because of their increased susceptibility to breast and uterine cervix cancer.