Journal
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
Volume 16, Issue 7, Pages 1096-1106Publisher
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.41246
Keywords
breast cancer; radiation; DNA damage repair; ATM
Categories
Funding
- National Natural Science Foundation of China [81970094]
- Program for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning [TP2015022]
- Shanghai Pujiang Program [15PJ1404800]
- Innovation Program of Shanghai Municipal Education Commission [15ZZ056]
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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.
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