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Epigenetic dysregulation of key developmental genes in radiation-induced rat mammary carcinomas
https://repo.qst.go.jp/records/49248
https://repo.qst.go.jp/records/4924802f91c59-7aa3-407f-afaf-54097e6208c3
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2018-02-13 | |||||
| タイトル | ||||||
| タイトル | Epigenetic dysregulation of key developmental genes in radiation-induced rat mammary carcinomas | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
Daino, Kazuhiro
× Daino, Kazuhiro× Nishimura, Mayumi× Imaoka, Tatsuhiko× Takabatake, Masaru× Morioka, Takamitsu× Nishimura, Yukiko× Shimada, Yoshiya× Kakinuma, Shizuko× Daino, Kazuhiro× Nishimura, Mayumi× Imaoka, Tatsuhiko× Takabatake, Masaru× Morioka, Takamitsu× Nishimura, Yukiko× Shimada, Yoshiya× Kakinuma, Shizuko |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | With the increase in the number of long-term cancer survivors worldwide, there is a growing concern about the risk of secondary cancers induced by radiotherapy. Epigenetic modifications of genes associated with carcinogenesis are attractive targets for the prevention of cancer owing to their reversible nature. To identify genes with possible changes in functionally relevant DNA methylation patterns in mammary carcinomas induced by radiation exposure, we performed microarray-based global DNA methylation and expression profiling in γ-ray-induced rat mammary carcinomas and normal mammary glands. The gene expression profiling identified dysregulation of developmentally related genes, including the downstream targets of polycomb repressive complex 2 (PRC2) and overexpression of enhancer of zeste homolog 2, a component of PRC2, in the carcinomas. By integrating expression and DNA methylation profiles, we identified 10 hypermethylated and three hypomethylated genes that possibly act as tumor-suppressor genes and oncogenes dysregulated by aberrant DNA methylation; half of these genes encode developmental transcription factors. Bisulfite sequencing and quantitative PCR confirmed the dysregulation of the polycomb-regulated developmentally related transcription-factor genes Dmrt2, Hoxa7, Foxb1, Sox17, Lhx8, Gata3, and Runx1. Silencing of Hoxa7 was further verified by immunohistochemistry. These results suggest that, in radiation-induced mammary gland carcinomas, PRC2-mediated aberrant DNA methylation leads to dysregulation of developmentally related transcription-factor genes. Our findings provide clues to molecular mechanisms linking epigenetic regulation and radiation-induced breast carcinogenesis and underscore the potential of such epigenetic mechanisms as targets for cancer prevention. | |||||
| 書誌情報 |
International Journal of Cancer 巻 143, 号 2, p. 343-354, 発行日 2018-02 |
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| 出版者 | ||||||
| 出版者 | Wiley | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0020-7136 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 29435983 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1002/ijc.31309 | |||||
