@article{von:2014:10.1038/ncb2916,
author = {von, Figura G and Fukuda, A and Roy, N and Liku, ME and Morris, JP and Kim, GE and Russ, HA and Firpo, MA and Mulvihill, SJ and Dawson, DW and Ferrer, J and Mueller, WF and Busch, A and Hertel, KJ and Hebrok, M},
doi = {10.1038/ncb2916},
journal = {Nature Cell Biology},
pages = {255--267},
title = {The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma},
url = {http://dx.doi.org/10.1038/ncb2916},
volume = {16},
year = {2014}
}

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TY  - JOUR
AB  - Pancreatic ductal adenocarcinoma (PDA) develops through distinct precursor lesions, including pancreatic intraepithelial neoplasia (PanIN) and intraductal papillary mucinous neoplasia (IPMN). However, genetic features resulting in IPMN-associated PDA (IPMN–PDA) versus PanIN-associated PDA (PanIN-PDA) are largely unknown. Here we find that loss of Brg1, a core subunit of SWI/SNF chromatin remodelling complexes, cooperates with oncogenic Kras to form cystic neoplastic lesions that resemble human IPMN and progress to PDA. Although Brg1-null IPMN–PDA develops rapidly, it possesses a distinct transcriptional profile compared with PanIN-PDA driven by mutant Kras and hemizygous p53 deletion. IPMN–PDA also is less lethal, mirroring prognostic trends in PDA patients. In addition, Brg1 deletion inhibits Kras-dependent PanIN development from adult acinar cells, but promotes Kras-driven preneoplastic transformation in adult duct cells. Therefore, this study implicates Brg1 as a determinant of context-dependent Kras-driven pancreatic tumorigenesis and suggests that chromatin remodelling may underlie the development of distinct PDA subsets.
AU  - von,Figura G
AU  - Fukuda,A
AU  - Roy,N
AU  - Liku,ME
AU  - Morris,JP
AU  - Kim,GE
AU  - Russ,HA
AU  - Firpo,MA
AU  - Mulvihill,SJ
AU  - Dawson,DW
AU  - Ferrer,J
AU  - Mueller,WF
AU  - Busch,A
AU  - Hertel,KJ
AU  - Hebrok,M
DO  - 10.1038/ncb2916
EP  - 267
PY  - 2014///
SN  - 1476-4679
SP  - 255
TI  - The chromatin regulator Brg1 suppresses formation of intraductal papillary mucinous neoplasm and pancreatic ductal adenocarcinoma
T2  - Nature Cell Biology
UR  - http://dx.doi.org/10.1038/ncb2916
UR  - http://hdl.handle.net/10044/1/38933
VL  - 16
ER  - 

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