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

First Author  Hingorani SR Year  2003
Journal  Cancer Cell Volume  4
Issue  6 Pages  437-50
PubMed ID  14706336 Mgi Jnum  J:87973
Mgi Id  MGI:3028768 Doi  10.1016/s1535-6108(03)00309-x
Citation  Hingorani SR, et al. (2003) Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell 4(6):437-50
abstractText  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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