Expression of the DNA-dependent protein kinase catalytic subunit is associated with the radiosensitivity of human thyroid cancer cell lines

被引:31
作者
Ihara, Makoto [1 ]
Ashizawa, Kiyoto [1 ,3 ]
Shichijo, Kazuko [2 ]
Kudo, Takashi [1 ]
机构
[1] Nagasaki Univ, Atom Bomb Dis Inst, Dept Radioisotope Med, Atom Bomb Dis & Hibakusha Med Unit, 1-12-4 Sakamoto, Nagasaki, Nagasaki 8528523, Japan
[2] Nagasaki Univ, Atom Bomb Dis Inst, Dept Tumor & Diagnost Pathol, Atom Bomb Dis & Hibakusha Med Unit, 1-12-4 Sakamoto, Nagasaki, Nagasaki 8528523, Japan
[3] Saiseikai Nagasaki Hosp, Dept Internal Med, 2-5-1 Katafuchi, Nagasaki, Nagasaki 8500003, Japan
基金
日本学术振兴会;
关键词
thyroid cancer cell; radiosensitivity; DNA-dependent protein kinase activity; DNA-dependent protein kinase catalytic subunit; predictive assay; DOUBLE-STRAND BREAKS; ESOPHAGEAL CANCER; HOMOLOGOUS RECOMBINATION; RADIATION SENSITIVITY; IONIZING-RADIATION; PKCS EXPRESSION; REPAIR; RADIOTHERAPY; INHIBITION; CARCINOMA;
D O I
10.1093/jrr/rry097
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
The prognosis and treatment of thyroid cancer depends on the type and stage of the disease. Radiosensitivity differs among cancer cells owing to their varying capacity for repair after irradiation. Radioactive iodine can be used to destroy thyroid cancer cells. However, patient prognosis and improvement after irradiation varies. Therefore, predictive measures are important for avoiding unnecessary exposure to radiation. We describe a new method for predicting the effects of radiation in individual cases of thyroid cancer based on the DNA-dependent protein kinase (DNA-PK) activity level in cancer cells. The radiation sensitivity, DNA-PK activity, and cellular levels of DNA-PK complex subunits in five human thyroid cancer cell lines were analyzed in vitro. A positive correlation was observed between the D-10 value (radiation dose that led to 10% survival) of cells and DNA-PK activity. This correlation was not observed after treatment with NU7441, a DNA-PK-specific inhibitor. A significant correlation was also observed between DNA-PK activity and expression levels of the DNA-PK catalytic subunit (DNA-PKcs). Cells expressing low DNA-PKcs levels were radiation-sensitive, and cells expressing high DNA-PKcs levels were radiation-resistant. Our results indicate that radiosensitivity depends on the expression level of DNA-PKcs in thyroid cancer cell lines. Thus, the DNA-PKcs expression level is a potential predictive marker of the success of radiation therapy for thyroid tumors.
引用
收藏
页码:171 / 177
页数:7
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