Acute pancreatitis accelerates initiation and progression to pancreatic cancer in mice expressing oncogenic Kras in the Nestin cell lineage

Catherine Carrière, Alison L. Young, Jason R. Gunn, Daniel S. Longnecker, Murray Korc

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Article numbere27725
JournalPloS one
Volume6
Issue number11
DOIs
StatePublished - Nov 28 2011

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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