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  1. 医歯学総合研究科
  2. 医歯学総合研究科・学術誌論文

Expression of MUC17 Is Regulated by HIF1a-Mediated

http://hdl.handle.net/10232/21458
http://hdl.handle.net/10232/21458
546aba50-4ae1-46aa-9b83-d0361e263bbc
名前 / ファイル ライセンス アクション
journal.pone.0044108.pdf journal.pone.0044108.pdf (1.8 MB)
Item type 学術雑誌論文 / Journal Article(1)
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

WEKO 117092

en Kitamoto, Sho

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横山, 勢也

× 横山, 勢也

WEKO 28537
NRID 1000020569941

ja 横山, 勢也

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東, 美智代

× 東, 美智代

WEKO 28538
NRID 1000060315405

ja 東, 美智代

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Yamada, Norishige

× Yamada, Norishige

WEKO 117093

en Yamada, Norishige

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松原, 修一郎

× 松原, 修一郎

WEKO 28540
NRID 1000060199841

ja 松原, 修一郎

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高尾, 尊身

× 高尾, 尊身

WEKO 3891
NRID 1000080171411

ja 高尾, 尊身

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Batra, Surinder K

× Batra, Surinder K

WEKO 117094

en Batra, Surinder K

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米澤, 傑

× 米澤, 傑

WEKO 28542
NRID 1000010175002

ja 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
アクセス権
アクセス権 open access
アクセス権URI http://purl.org/coar/access_right/c_abf2
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 2012-09-10
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
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