The Nestin progenitor lineage is the compartment of origin for pancreatic intraepithelial neoplasia

Catherine Carrière, Elliott S. Seeley, Tobias Goetze, Daniel S. Longnecker, Murray Korc

Research output: Contribution to journalArticle

96 Scopus citations

Abstract

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 (KrasG12D) 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 KrasG12D 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.

Original languageEnglish (US)
Pages (from-to)4437-4442
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume104
Issue number11
DOIs
StatePublished - Mar 13 2007

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Keywords

  • Cell of origin
  • Kras
  • Pancreatic ductal adenocarcinoma

ASJC Scopus subject areas

  • General

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