Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] · 2013
The conditional expression of KRAS G12D in mouse pancreas induces disorganization of endocrine islets prior the onset of ductal pre-cancerous lesions.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Gout Johann, Pommier Roxane M, Vincent David F, Ripoche Doriane, Goddard-Léon Sophie, Colombe Amélie, Treilleux Isabelle, Valcourt Ulrich, Tomasini Richard, Dufresne Marlène, Bertolino Philippe, Bartholin Laurent
Аннотация
BACKGROUND/OBJECTIVES: 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.
METHODS: We examined by histology whether Pdx1-driven expression of KRAS(G12D) could induce islets of Langerhans defects.
RESULTS: 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.
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.
METHODS: We examined by histology whether Pdx1-driven expression of KRAS(G12D) could induce islets of Langerhans defects.
RESULTS: 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.
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.