9
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      Ataxia‐telangiectasia mutated (ATM) participates in the regulation of ionizing radiation‐induced cell death via MAPK14 in lung cancer H1299 cells

      research-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objectives

          The role of Ataxia‐telangiectasia mutated ( ATM) in response to DNA damage has previously been studied, but its underlying mechanisms specific to ionizing radiation ( IR) have remained to be elucidated. In this study, function of ATM on radiation‐induced cell death in lung cancer H1299 cells was analysed.

          Materials and methods

          Human lung cancer cells, H1299, were used, and cell models with ATM −/− and MAPK14 −/− were established by genetic engineering. Radiosensitivity was analysed using colony formation assays. Western blotting and co‐immunoprecipitation were implemented to detect protein expression and interaction. MDC staining and GFPLC3 relocalization were used to detect autophagy.

          Results

          Autophagy as well as phosphorylation of ATM was activated by ionizing radiation. Both the inhibitor of ATM, KU55933 and ATM silencing reduced phosphorylation of ATM and MAPKAPK2 expression. Both ATM −/− and MAPK14 −/− cells displayed hypersensitivity. IR increased autophagy level by more than 129% in DMSO‐treated cells, while only by 47% and 27% in KU55933‐treated and ATM −/− cells respectively. MAPK14 knock‐down alone gave rise to the basal autophagy level, but decreased notably after IR. KU55933 and ATM knock‐down inhibited IR‐induced autophagy by activating mTOR pathways. Both Beclin1– PI3 KIII and Beclin1– MAPKAPK2 interactions as were remarkably affected by silencing either ATM or MAPK14.

          Conclusions

          ATM promoted IR‐induced autophagy via the MAPK14 pathway, mTOR pathway and Beclin1/ PI3 KIII complexes. MAPK14 contributed to radiosensitization of H1299 cells.

          Related collections

          Author and article information

          Journal
          Cell Prolif
          Cell Prolif
          10.1111/(ISSN)1365-2184
          CPR
          Cell Proliferation
          John Wiley and Sons Inc. (Hoboken )
          0960-7722
          1365-2184
          13 August 2015
          October 2015
          : 48
          : 5 ( doiID: 10.1111/cpr.2015.48.issue-5 )
          : 561-572
          Affiliations
          [ 1 ] Key Laboratory of Radiobiology (Ministry of Health) School of Public Health Jilin University Changchun 130021 China
          [ 2 ] University of Manitoba Winnipeg Manitoba R3E 0V9 Canada
          [ 3 ] Department of Radiation Oncology 1st Hospital Affiliated to Jilin University Changchun 130021 China
          [ 4 ] University of Manitoba Manitoba Institute of Cell Biology Winnipeg Manitoba R3E 0V9 Canada
          [ 5 ] Department of Radiation Oncology China‐Japan Union Hospital of Jilin University Changchun 130021 China
          Author notes
          [*] [* ]Correspondence: Xiaodong Liu, 1163 Xinmin Street, Changchun, Jilin 130021, China. Tel.:  86 431 85619418; Fax: +86 431 85619418; E‐mail: liuxd2014@ 123456126.com and Guanghui Cheng, 126 Xiantai Street, Changchun, Jilin 130033, China. Tel.: +86 431 85619418; Fax: +86 431 85619418; E‐mail: 827229953@ 123456qq.com
          Article
          PMC6496706 PMC6496706 6496706 CPR12203
          10.1111/cpr.12203
          6496706
          26269117
          8966236b-0103-453c-a9f3-92b4a828ca3f
          © 2015 John Wiley & Sons Ltd
          History
          : 28 April 2015
          : 20 June 2015
          Page count
          Pages: 12
          Funding
          Funded by: NSFC
          Award ID: 30770649
          Award ID: 30970682
          Award ID: 31370837
          Funded by: Research Fund for the Doctoral Program of Higher Education of China
          Award ID: 20100061110070
          Funded by: Program for New Century Excellent Talents in University
          Funded by: Fundamental Research Funds for the Jilin University
          Categories
          Original Article
          Original Articles
          Custom metadata
          2.0
          cpr12203
          October 2015
          Converter:WILEY_ML3GV2_TO_NLMPMC version:5.6.2.1 mode:remove_FC converted:02.05.2019

          Comments

          Comment on this article