Chronic pancreatitis is essential for induction of pancreatic ductal adenocarcinoma by K-Ras oncogenes in adult mice

Cancer Cell. 2007 Mar;11(3):291-302. doi: 10.1016/j.ccr.2007.01.012.


Pancreatic ductal adenocarcinoma (PDA), one of the deadliest human cancers, often involves somatic activation of K-Ras oncogenes. We report that selective expression of an endogenous K-Ras(G12V) oncogene in embryonic cells of acinar/centroacinar lineage results in pancreatic intraepithelial neoplasias (PanINs) and invasive PDA, suggesting that PDA originates by differentiation of acinar/centroacinar cells or their precursors into ductal-like cells. Surprisingly, adult mice become refractory to K-Ras(G12V)-induced PanINs and PDA. However, if these mice are challenged with a mild form of chronic pancreatitis, they develop the full spectrum of PanINs and invasive PDA. These observations suggest that, during adulthood, PDA stems from a combination of genetic (e.g., somatic K-Ras mutations) and nongenetic (e.g., tissue damage) events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology*
  • Cell Lineage
  • Cell Transformation, Neoplastic
  • Ceruletide
  • Doxycycline / pharmacology
  • Genes, ras*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / secondary
  • Mice
  • Mice, Mutant Strains
  • Mutation
  • Neoplasm Invasiveness
  • Pancreas / pathology
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology*
  • Pancreatitis, Chronic / chemically induced
  • Pancreatitis, Chronic / pathology*
  • Signal Transduction


  • Ceruletide
  • Doxycycline