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Gout J.,TGF and Pancreatic Cancer Laboratory | Gout J.,French Institute of Health and Medical Research | Gout J.,French National Center for Scientific Research | Gout J.,University of Lyon | And 38 more authors.

Background/objectives: Pdx1-Cre; LSL-KRASG12D mice develop premalignant pancreatic ductal lesions that can possibly progress spontaneously to pancreatic ductal adenocarcinoma (PDAC). Although Pdx1-Cre is expressed in the embryonic endoderm, which gives rise to all pancreatic lineages, the possible consequences of KRASG12D expression in the endocrine compartment have never been finely explored. Methods: We examined by histology whether Pdx1-driven expression of KRASG12D could induce islets of Langerhans defects. Results: We observed in Pdx1-Cre; LSL-KRASG12D early disorganization of the endocrine compartment including i) hyperplasia affecting all the endocrine lineages, ii) ectopic onset of Ck19-positive (ductal-like) structures within the endocrine islets, and iii) the presence of islet cells co-expressing glucagon and insulin, all occurring before the onset of ducts lesions. Conclusions: This work indicates that expression of KRAS G12D in Pdx1-expressing cells during embryogenesis affects the endocrine pancreas, and highlights the need to deepen possible consequences on both glucose metabolism and PDAC initiation. Copyright © 2013, IAP and EPC. Published by Elsevier India, a division of Reed Elsevier India Pvt. Ltd. All rights reserved. Source

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