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

• Published in: International journal of biological sciences Vol. 16; no. 7; pp. 1096 - 1106
• Main Authors: Bian, Lei, Meng, Yiling, Zhang, Meichao, Guo, Zhuying, Liu, Furao, Zhang, Weiwen, Ke, Xue, Su, Yuxuan, Wang, Meng, Yao, Yuan, Wu, Lizhong, Li, Dong
• Format: Journal Article
• Language: English
• Published: Australia Ivyspring International Publisher Pty Ltd 01.01.2020; Ivyspring International Publisher
• Subjects: Apoptosis; Ataxia; Ataxia Telangiectasia Mutated Proteins - genetics; Ataxia Telangiectasia Mutated Proteins - metabolism; Blotting, Western; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Cancer therapies; Cell cycle; Cell Line, Tumor; Chemotherapy; Deoxyribonucleic acid; DNA; DNA Breaks, Double-Stranded - radiation effects; DNA damage; DNA Damage - genetics; DNA Damage - radiation effects; DNA repair; DNA Repair - genetics; DNA Repair - radiation effects; Double-strand break repair; Efficiency; Enzymes; Flow Cytometry; Gene expression; Homologous recombination; Homology; Humans; Ionizing radiation; Kinases; Malignancy; Non-homologous end joining; Plasmids; Radiation damage; Radiation therapy; Radiation Tolerance; Radiation, Ionizing; Radioresistance; Radiosensitivity; Reagents; Repair; Research Paper; DNA damage repair; breast cancer; ATM; radiation
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.41246

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 γ-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.