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タイトル: Context-Dependent Roles of Hes1 in the Adult Pancreas and Pancreatic Tumor Formation
著者: Marui, Saiko
Nishikawa, Yoshihiro  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-1113-6937 (unconfirmed)
Shiokawa, Masahiro  kyouindb  KAKEN_id
Yokode, Masataka
Matsumoto, Shimpei
Muramoto, Yuya
Ota, Sakiko
Nakamura, Takeharu
Yoshida, Hiroyuki
Okada, Hirokazu
Kuwada, Takeshi
Matsumori, Tomoaki
Kuriyama, Katsutoshi
Fukuda, Akihisa  kyouindb  KAKEN_id
Saur, Dieter
Aoi, Takashi
Uza, Norimitsu  KAKEN_id
Kodama, Yuzo
Chiba, Tsutomu
Seno, Hiroshi  kyouindb  KAKEN_id
著者名の別形: 丸井, 彩子
西川, 義浩
塩川, 雅広
横出, 正隆
松本, 慎平
村本, 雄哉
太田, 彩貴子
中村, 武晴
吉田, 裕幸
岡田, 浩和
桒田, 威
松森, 友昭
栗山, 勝利
福田, 晃久
宇座, 徳光
妹尾, 浩
キーワード: Pancreatic Ductal Adenocarcinoma
PanIN
Muc5ac
Notch
発行日: Dec-2022
出版者: Elsevier BV
AGA Institute
誌名: Gastroenterology
巻: 163
号: 6
開始ページ: 1613
終了ページ: 1629
論文番号: e12
抄録: [Background & Aims] The Notch signaling pathway is an important pathway in the adult pancreas and in pancreatic ductal adenocarcinoma (PDAC), with hairy and enhancer of split-1 (HES1) as the core molecule in this pathway. However, the roles of HES1 in the adult pancreas and PDAC formation remain controversial. [Methods] We used genetically engineered dual-recombinase mouse models for inducing Hes1 deletion under various conditions. [Results] The loss of Hes1 expression in the adult pancreas did not induce phenotypic alterations. However, regeneration was impaired after caerulein-induced acute pancreatitis. In a pancreatic intraepithelial neoplasia (PanIN) mouse model, PanINs rarely formed when Hes1 deletion preceded PanIN formation, whereas more PanINs were formed when Hes1 deletion succeeded PanIN formation. In a PDAC mouse model, PDAC formation was also enhanced by Hes1 deletion after PanIN/PDAC development; therefore, Hes1 promotes PanIN initiation but inhibits PanIN/PDAC progression. RNA sequencing and chromatin immunoprecipitation-quantitative polymerase chain reaction revealed that Hes1 deletion enhanced epithelial-to-mesenchymal transition via Muc5ac up-regulation in PDAC progression. The results indicated that HES1 is not required for maintaining the adult pancreas under normal conditions, but is important for regeneration during recovery from pancreatitis; moreover, Hes1 plays different roles, depending on the tumor condition. [Conclusions] Our findings highlight the context-dependent roles of HES1 in the adult pancreas and pancreatic cancer.
著作権等: © 2022 The Author(s). Published by Elsevier Inc. on behalf of the AGA Institute.
This is an open access article under the CC BY license.
URI: http://hdl.handle.net/2433/279490
DOI(出版社版): 10.1053/j.gastro.2022.08.048
PubMed ID: 36075324
出現コレクション:学術雑誌掲載論文等

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