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      Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse.

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          Abstract

          To evaluate the role of oncogenic RAS mutations in pancreatic tumorigenesis, we directed endogenous expression of KRAS(G12D) to progenitor cells of the mouse pancreas. We find that physiological levels of Kras(G12D) induce ductal lesions that recapitulate the full spectrum of human pancreatic intraepithelial neoplasias (PanINs), putative precursors to invasive pancreatic cancer. The PanINs are highly proliferative, show evidence of histological progression, and activate signaling pathways normally quiescent in ductal epithelium, suggesting potential therapeutic and chemopreventive targets for the cognate human condition. At low frequency, these lesions also progress spontaneously to invasive and metastatic adenocarcinomas, establishing PanINs as definitive precursors to the invasive disease. Finally, mice with PanINs have an identifiable serum proteomic signature, suggesting a means of detecting the preinvasive state in patients.

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          Author and article information

          Journal
          Cancer Cell
          Cancer cell
          Elsevier BV
          1535-6108
          1535-6108
          Dec 2003
          : 4
          : 6
          Affiliations
          [1 ] Department of Medicine, Abramson Family Cancer Research Institute, Abramson Center at the University of Pennsylvania, Philadelphia, PA 19104, USA.
          Article
          S153561080300309X
          10.1016/s1535-6108(03)00309-x
          14706336
          84a2f3ec-a30e-4db2-95ed-83024791f357
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