ATM Expression Is Elevated in Established Radiation-Resistant Breast Cancer Cells and Improves DNA Repair Efficiency
| Autor: | Yiling Meng, Meng Wang, Lizhong Wu, Yuan Yao, Lei Bian, Yuxuan Su, Furao Liu, Zhuying Guo, Meichao Zhang, Weiwen Zhang, Dong Li, Xue Ke |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
DNA Repair
DNA repair medicine.medical_treatment Blotting Western Breast Neoplasms Ataxia Telangiectasia Mutated Proteins Applied Microbiology and Biotechnology Radiation Tolerance 03 medical and health sciences breast cancer Radioresistance Cell Line Tumor Radiation Ionizing medicine Humans DNA damage repair DNA Breaks Double-Stranded Radiosensitivity Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology 0303 health sciences Gene knockdown Chemistry Cell Biology DNA Repair Pathway Flow Cytometry Radiation therapy radiation ATM Cancer cell Cancer research Homologous recombination Developmental Biology DNA Damage Research Paper |
| Zdroj: | International Journal of Biological Sciences |
| ISSN: | 1449-2288 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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