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The Conditional Expression of KRASG12D in Mouse Pancreas Induces Disorganization of Endocrine Islets Prior the Onset of Ductal Pre-cancerous Lesions


, : The Conditional Expression of KRASG12D in Mouse Pancreas Induces Disorganization of Endocrine Islets Prior the Onset of Ductal Pre-cancerous Lesions. Pancreatology 13(3): 191-195

Pdx1-Cre;LSL-KRAS G12D 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 KRAS G12D expression in the endocrine compartment have never been finely explored. We examined by histology whether Pdx1-driven expression of KRAS G12D could induce islet of Langerhans defects. We observed in Pdx1-Cre;LSL-KRAS G12D 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. 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.

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