Proceedings of the National Academy of Sciences of the United States of America
To determine the cell compartment in which initial oncogenic mutations occur in pancreatic ductal adenocarcinoma (PDAC), we generated a mouse model in which endogenous expression of mutated Kras (Kras(G12D)) was initially directed to a population of pancreatic exocrine progenitors characterized by the expression of Nestin. Targeting of oncogenic Kras to such a restricted cell compartment was sufficient for the formation of pancreatic intraepithelial neoplasias (PanINs), putative precursors to PDAC. PanINs appeared with the same grade and frequency as observed when Kras(G12D) was targeted to the whole pancreas by a Pdx1-driven Cre recombinase strategy. Thus, the Nestin cell lineage is highly responsive to Kras oncogenic activation and may represent the elusive progenitor population in which PDAC arises.
Carriere, Catherine; Seeley, Elliot S.; Goetze, Tobias; Longnecker, Daniel S.; and Korc, Murray, "The Nestin Progenitor Lineage is the Compartment of Origin for Pancreatic Intraepithelial Neoplasia" (2007). Open Dartmouth: Faculty Open Access Articles. 1423.