Radiation induces autophagic cell death via the p53/DRAM signaling pathway in breast cancer cells

Cui,Li; Song,Zhiheng; Liang,Bing; Jia,Lili; Ma,Shumei; Liu,Xiaodong

doi:10.3892/or.2016.4752

Radiation induces autophagic cell death via the p53/DRAM signaling pathway in breast cancer cells

Authors:
- Li Cui
- Zhiheng Song
- Bing Liang
- Lili Jia
- Shumei Ma
- Xiaodong Liu
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Affiliations: Key Laboratory of Radiobiology (Ministry of Health), School of Public Health, Jilin University, Changchun, Jilin 130021, P.R. China, Jilin Province People's Hospital, Changchun, Jilin 130021, P.R. China
Published online on: April 19, 2016 https://doi.org/10.3892/or.2016.4752
Pages: 3639-3647

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Abstract

Autophagy is known to play a role in the response of breast cancer cells to radiation therapy. However, the mechanisms that mediate the process of autophagy and contribute to radiation-induced cell death and cell survival remain to be fully characterized. Therefore, in this study, the functional role of autophagy in radiation-induced cytotoxicity in breast cancer cells was investigated. After MCF-7 cells were exposed to various doses of radiation, increased monodansylcadaverine (MDC) staining and a greater deposition of LC3-positive puncta were observed. Expression of the autophagy-related proteins, Beclin 1 and LC3-II, were also found to be upregulated. Radiation-induced autophagic cell death was partially abrogated following the administration of 3-methyladenine (3-MA) and in knockdown experiments of Atg5 and Beclin 1. In the gene microarray analysis performed after irradiation, a number of differentially expressed genes were identified. In particular, upregulation of both the mRNA and protein levels of the autophagy-related genes, DRAM and TIGAR, were detected. However, inhibition of autophagy by 3-MA reduced the radiation-induced upregulation of LC3-II and DRAM. Conversely, silencing of p53 downregulated the expression of LC3-II and DRAM following radiation. Silencing of DRAM reversed the upregulation of LC3-II and DRAM following radiation, partially blocked radiation-induced cell death, and no significant change in p53 expression was detected. Based on these results, the p53/DRAM signaling pathway appears to contribute to radiation-induced autophagic cell death in MCF-7 breast cancer cells.

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