Acute pancreatitis markedly accelerates pancreatic cancer progression in mice expressing oncogenic Kras.
Chronic pancreatitis increases by 16-fold the risk of developing pancreatic ductal adenocarcinoma (PDAC), one of the deadliest human cancers. It also appears to accelerate cancer progression in genetically engineered mouse models. We now report that in a mouse model where oncogenic Kras is activated in all pancreatic cell types, two brief episodes of acute pancreatitis caused rapid PanIN progression and accelerated pancreatic cancer development. Thus, a brief inflammatory insult to the pancreas, when occurring in the context of oncogenic Kras(G12D), can initiate a cascade of events that dramatically enhances the risk for pancreatic malignant transformation.
Carrière
Catherine
C
Department of Medicine, Dartmouth Medical School, Hanover, NH 03755, USA. Catherine.Carriere@Dartmouth.edu
Young
Alison L
AL
Gunn
Jason R
JR
Longnecker
Daniel S
DS
Korc
Murray
M
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D051379:Mice; D008815:Mice, Inbred Strains; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D010195:Pancreatitis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis* / Q000235:genetics
C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)