ATM Expression Is Elevated in Established Radiation-Resistant Breast Cancer Cells and Improves DNA Repair Efficiency

被引：37

作者：

Bian, Lei ^{[1
]}

Meng, Yiling ^{[1
]}

Zhang, Meichao ^{[1
]}

Guo, Zhuying ^{[2
]}

Liu, Furao ^{[1
]}

Zhang, Weiwen ^{[1
]}

Ke, Xue ^{[1
]}

Su, Yuxuan ^{[1
]}

Wang, Meng ^{[1
]}

Yao, Yuan ^{[1
]}

Wu, Lizhong ^{[3
]}

Li, Dong ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Shanghai Ninth Peoples Hosp, Dept Radiat Oncol, Sch Med, Shanghai, Peoples R China

[2] Shanghai Jiao Tong Univ, Shanghai Ninth Peoples Hosp, Dept Clin Lab, Sch Med, Shanghai, Peoples R China

[3] Shanghai Jiao Tong Univ, Shanghai Ninth Peoples Hosp, Dept Radiol, Sch Med, 280 Mohe Rd, Shanghai 201999, Peoples R China

来源：

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES | 2020年 / 16卷 / 07期

基金：

中国国家自然科学基金;

关键词：

breast cancer; radiation; DNA damage repair; ATM; DOUBLE-STRAND BREAKS; HOMOLOGOUS RECOMBINATION; IONIZING-RADIATION; KINASE; COMPLEX; PHOSPHORYLATION; RADIORESISTANCE; GAMMA-H2AX; RESPONSES; PK;

D O I：

10.7150/ijbs.41246

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Repair of damaged DNA induced by radiation plays an important role in the development of radioresistance, which greatly restricts patients' benefit from radiotherapy. However, the relation between radioresistance development and DNA double-strand break repair pathways (mainly non-homologous end joining and homologous recombination) and how these pathways contribute to radioresistance are unclear. Here, we established a radioresistant breast cancer cell line by repeated ionizing radiation and studied the alteration in DNA repair capacity. Compared with parental sham-treated cells, radioresistant breast cancer cells present elevated radioresistance, enhanced malignancy, increased expression of Ataxia-telangiectasia mutated (ATM), and increased DNA damage repair efficiency, as reflected by accelerated gamma-H2AX kinetic. These defects can be reversed by ATM inhibition or ATM knockdown, indicating a potential link between ATM, DNA repair pathway and radiosensitivity. We propose that cancer cells develop elevated radioresistance through enhanced DNA damage repair efficiency mediated by increased ATM expression. Our work might provide a new evidence supporting the potential of ATM as a potential target of cancer therapy.

引用

页码：1096 / 1106

页数：11

共 40 条

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