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논문 기본 정보

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학술저널
저자정보
Oh, Jung-Min (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Kim, Young-Eun (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Hong, Beom-Ju (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Bok, Seoyeon (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Jeon, Seong-Uk (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Lee, Chan-Ju (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Park, Dong-Young (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology) Kim, Il Han (Department of Radiation Oncology, College of Medicine, Seoul National University) Kim, Hak Jae (Department of Radiation Oncology, College of Medicine, Seoul National University) Ahn, G-One (Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology)
저널정보
대한방사선방어학회 방사선방어학회지 방사선방어학회지 제43권 제2호
발행연도
2018.1
수록면
66 - 74 (9page)

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Background: Tumor response to anticancer therapies can much be influenced by microenvironmental factors. In this study, we determined the effect of these microenvironmental factors on DNA methylation using A549 human lung adenocarcinoma cell line. Materials and Methods: We subjected A549 cells to various conditions mimicking tumor microenvironment including hypoxia, acidosis (sodium lactate), oxidative stress ($H_2O_2$), bystander effect (supernatant from doxorubicin (Dox)-treated or irradiated cells), and immune cell infiltration (supernatant from THP-1 or Jurkat T cells). Genomic DNA was isolated from these cells and analyzed for DNA methylation. Clonogenic cell survival, gene expression, and metabolism were analyzed in cells treated with some of these conditions. Results and Discussion: We found that DNA methylation level was significantly decreased in A549 cells treated with conditioned media from Dox-treated cells or Jurkat T cells, or sodium lactate, indicating an active transcription. To determine whether the decreased DNA methylation affects radiation sensitivity, we exposed cells to these conditions followed by 6 Gy irradiation and found that cell survival was significantly increased by sodium lactate while it was decreased by conditioned media from Dox-treated cells. We further observed that cells treated with conditioned media from Dox-treated cells exhibited significant changes in expression of genes including BAX and FAS (involved in apoptosis), NADPH dehydrogenase (mitochondria), EGFR (cellular survival) and RAD51 (DNA damage repair) while sodium lactate increased cellular metabolism rather than changing the gene expression. Conclusion: Our results suggest that various tumor microenvironmental factors can differentially influence DNA methylation and hence radiosensitivity and gene expression in A549 cancer cells.
#DNA methylation #Tumor microenvironment #Radiosensitivity #Gene expression #Metabolism

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참고문헌 (27)

참고문헌 신청
Brown JM / 2004 / Exploiting tumour hypoxia in cancer treatment / Nat. Rev. Cancer. 4(6):437~447 Crossref Franco M / 2011 / Pericytes promote endothelial cell survival through induction of autocrine VEGF-A signaling and Bcl-w expression / Blood 118(10):2906~2917 Crossref Gouaze-Andersson V / 2016 / FGFR1 Induces Glioblastoma radioresistance through the PLCgamma/Hif1alpha pathway / Cancer Res. 76(10):3036~3044 Crossref Ahn GO / 2008 / Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells / Cancer Cell. 13(3):193~205 Crossref Smits KM / 2014 / Epigenetics in radiotherapy: where are we heading? / Radiother. Oncol. 111(2):168~177 Crossref

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