title: Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the nestin cell lineage.
abstract: Targeting of oncogenic Kras to the pancreatic Nestin-expressing embryonic progenitor cells and subsequently to the adult acinar compartment and Nestin-expressing cells is sufficient for the development of low grade pancreatic intraepithelial neoplasia (PanIN) between 2 and 4 months. The mice die around 6 month-old of unrelated causes, and it is therefore not possible to assess whether the lesions will progress to carcinoma. We now report that two brief episodes of caerulein-induced acute pancreatitis in 2 month-old mice causes rapid PanIN progression and pancreatic ductal adenocarcinoma (PDAC) development by 4 months of age. These events occur with similar frequency as observed in animals where the oncogene is targeted during embryogenesis to all pancreatic cell types. Thus, these data show that oncogenic Kras-driven PanIN originating in a non-ductal compartment can rapidly progress to PDAC when subjected to a brief inflammatory insult.
authors.affiliation: Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, United States of America. Carriere@Dartmouth.edu
authors.forename: Catherine
authors.initials: C
authors.lastname: Carrière
authors.forename: Alison L
authors.initials: AL
authors.lastname: Young
authors.forename: Jason R
authors.initials: JR
authors.lastname: Gunn
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Longnecker
authors.forename: Murray
authors.initials: M
authors.lastname: Korc
mesh_terms: D000818:Animals; D002278:Carcinoma in Situ / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage; D002108:Ceruletide; D018450:Disease Progression; D018390:Gene Targeting; D006801:Humans; D019426:Integrases / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D064231:Nestin; D010183:Pancreatic Ducts / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology*; D011230:Precancerous Conditions / Q000378:metabolism / Q000473:pathology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D007381:Intermediate Filament Proteins; C577484:NES protein, human; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D050796:STAT3 Transcription Factor; D002108:Ceruletide; C045073:Cre recombinase; D019426:Integrases; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)