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Literature DB >> 17360542

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

Catherine Carrière¹, Elliott S Seeley, Tobias Goetze, Daniel S Longnecker, Murray Korc.

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 (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.

Entities: Chemical Disease Gene Mutation Species

Mesh：

Substances：

Year: 2007 PMID： 17360542 PMCID： PMC1810329 DOI： 10.1073/pnas.0701117104

Source DB: PubMed Journal: Proc Natl Acad Sci U S A ISSN： 0027-8424 Impact factor: 11.205

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