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Expression of MUC17 Is Regulated by HIF1a-Mediated
http://hdl.handle.net/10232/21458
http://hdl.handle.net/10232/21458546aba50-4ae1-46aa-9b83-d0361e263bbc
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
journal.pone.0044108.pdf (1.8 MB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2014-12-22 | |||||
| タイトル | ||||||
| タイトル | Expression of MUC17 Is Regulated by HIF1a-Mediated | |||||
| タイトル言語 | en | |||||
| 著者 |
Kitamoto, Sho
× Kitamoto, Sho× 横山, 勢也× 東, 美智代× Yamada, Norishige× 松原, 修一郎× 高尾, 尊身× Batra, Surinder K× 米澤, 傑 |
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| 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 | |||||
| 要約 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | MUC17 is a type 1 membrane-bound glycoprotein that is mainly expressed in the digestive tract. Recent studies have demonstrated that the aberrant overexpression of MUC17 is correlated with the malignant potential of pancreatic ductal adenocarcinomas (PDACs); however, the exact regulatory mechanism of MUC17 expression has yet to be identified. Here, we provide the first report of the MUC17 regulatory mechanism under hypoxia, an essential feature of the tumor microenvironment and a driving force of cancer progression. Our data revealed that MUC17 was significantly induced by hypoxic stimulation through a hypoxia-inducible factor 1a (HIF1a)-dependent pathway in some pancreatic cancer cells (e.g., AsPC1), whereas other pancreatic cancer cells (e.g., BxPC3) exhibited little response to hypoxia. Interestingly, these lowresponsive cells have highly methylated CpG motifs within the hypoxia responsive element (HRE, 59-RCGTG-39), a binding site for HIF1a. Thus, we investigated the demethylation effects of CpG at HRE on the hypoxic induction of MUC17. Treatment of low-responsive cells with 5-aza-29-deoxycytidine followed by additional hypoxic incubation resulted in the restoration of hypoxic MUC17 induction. Furthermore, DNA methylation of HRE in pancreatic tissues from patients with PDACs showed higher hypomethylation status as compared to those from non-cancerous tissues, and hypomethylation was also correlated with MUC17 mRNA expression. Taken together, these findings suggested that the HIF1a-mediated hypoxic signal pathway contributes to MUC17 expression, and DNA methylation of HRE could be a determinant of the hypoxic inducibility of MUC17 in pancreatic cancer cells. | |||||
| 内容記述言語 | en | |||||
| 収録雑誌名 |
en : PLoS ONE 巻 7, 号 9, p. e44108, 発行日 2012 |
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| 作成日 | ||||||
| 日付 | 2012-09-10 | |||||
| 日付タイプ | Issued | |||||
| ISSN | ||||||
| 収録物識別子タイプ | EISSN | |||||
| ISSN | 19326203 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| DOI | https://doi.org/10.1371/journal.pone.0044108 | |||||
| 出版タイプ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| NDC | ||||||
| 主題Scheme | NDC | |||||
| 主題 | 493.475 | |||||
| 公開者・出版者 | ||||||
| 出版者 | Public Library of Science | |||||
| 出版者言語 | en | |||||
