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

Abstract

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.

Identification of Radiotherapy-Associated Genes in Lung Adenocarcinoma by an Integrated Bioinformatics Analysis Approach

“…To find the difference between the RR and RS groups, we utilized GSVA to distinguish the biological function of the RR and RS samples (Figure 2A). Based on GSVA analysis, we found that the functional difference between RS and RR patients was associated with extracellular matrix (ECM) and DNA-related functions, which was consistent with previous reports (Ljungman, 2009;Bian et al, 2020;Haeger et al, 2020). Interestingly, two immune-related terms, immunoglobulin receptor binding and CD22-mediated BCR regulation (Figure 2A), were observed in the list of the top 25 terms enriched in the RR or RS groups, indicating that the immune microenvironment is involved in the RT response.…”

Space Radiation Protection Countermeasures in Microgravity and Planetary Exploration

“…These two main DSBs repair pathways play an indispensable role in initiating and processing cancer. Patients harboring deficiencies affecting HR or NHEJ often present increased susceptibility towards cancer [ 127 , 145 , 146 , 147 ].…”

“…For radiation-inducing cytotoxic activity of CD8+ T cells through the release cytotoxic proteins, the principal mechanism through which cytotoxic T cells act is by the calcium-dependent release of specialized lytic granules upon recognition of antigen on the surface of a target cell. These granules are modified lysosomes that contain at least two distinct classes of cytotoxic effector protein that are expressed selectively in cytotoxic T cells [ 147 ].…”

Role of miRNAs in regulating responses to radiotherapy in human breast cancer

“…This might contribute to radioresistance as the arrest in the cell cycle provides time for the damaged DNA to be repaired, allowing cancer cells to continue proliferating (Gogineni et al 2011;. Therefore, radioresistant cancer cells can also exhibit enhanced DNA damage repair capacity, as evidenced by the upregulation of key genes involved in DNA repair pathways such as Chk1 (Jiang et al 2019), ATM (Bian et al 2020), RAD1, BRCA1, and BRCA2 (Balbous et al 2016).…”