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

Citations Over TimeTop 10% of 2016 papers

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.

Related Papers

• → Methods for Assessing Autophagy and Autophagic Cell Death(2008)187 cited
• → The Rab GTPase RabG3b functions in autophagy and contributes to tracheary element differentiation in Arabidopsis(2010)167 cited
• → Autophagy in Cell Life and Cell Death(2015)156 cited
• → Apoptosis regulation by autophagy gene 5(2007)55 cited
• → Rhabdastrellic Acid-A Induced Autophagy-Associated Cell Death through Blocking Akt Pathway in Human Cancer Cells(2010)33 cited