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Title: Molecular mechanism of intraductal papillary mucinous neoplasm and intraductal papillary mucinous neoplasm-derived pancreatic ductal adenocarcinoma.
Authors: Fukuda, Akihisa  kyouindb  KAKEN_id
Author's alias: 福田, 晃久
Keywords: Cellular origin
Chromatin remodeling
Intraductal papillary mucinous neoplasia
Mouse model
Pancreatic cancer
Issue Date: 21-Apr-2015
Publisher: wiley
Journal title: Journal of hepato-biliary-pancreatic sciences
Volume: 22
Issue: 7
Start page: 519
End page: 523
Abstract: Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal human malignancies. Dissecting the mechanisms underlying PDA development is important for developing early detection methods and effective prevention and therapies for the disease. PDA is considered to arise from distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, little is known about molecular mechanisms of development of IPMN and IPMN-derived PDA. We have recently reported that loss of Brg1, a core subunit of SWI/SNF chromatin remodeling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA. Brg1 null IPMN-PDA is less lethal compared to PanIN-derived PDA (PanIN-PDA) driven by mutant Kras and hemizygous p53 deletion, mirroring prognostic trends in PDA patients. Brg1 null IPMN-PDA possesses a distinct molecular signature that supports less malignant potential compared to PanIN-PDA. Furthermore, Brg1 deletion inhibits Kras-dependent PanIN development from adult acinar cells, but promotes Kras-driven preneoplastic transformation in adult duct cells. Therefore, Brg1 is a determinant of context-dependent Kras-driven pancreatic tumorigenesis and chromatin remodeling may underlie the development of distinct PDA subsets. Understanding molecular mechanism of IPMN and IPMN-derived PDA could provide critical clues for novel diagnostic and therapeutic strategies of the disease.
Rights: This is the peer reviewed version of the following article: Fukuda, A. (2015) Molecular mechanism of intraductal papillary mucinous neoplasm and intraductal papillary mucinous neoplasm-derived pancreatic ductal adenocarcinoma. J Hepatobiliary Pancreat Sci, 22: 519–523, which has been published in final form at http://dx.doi.org/10.1002/jhbp.246. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
The full-text file will be made open to the public on 21 April 2016 in accordance with publisher's 'Terms and Conditions for Self-Archiving'.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。This is not the published version. Please cite only the published version.
URI: http://hdl.handle.net/2433/201971
DOI(Published Version): 10.1002/jhbp.246
PubMed ID: 25900667
Appears in Collections:Journal Articles

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