Characterization of Kras-mediated pancreatic tumorigenesis in zebrafish.
Activating Kras mutations are a pervasive and characteristic feature of human pancreatic cancer. In order to examine the earliest in vivo effects of oncogenic Kras expression in the exocrine pancreas, we generated two lines of zebrafish expressing eGFP alone or eGFP fused to human Kras with an activating mutation in codon 12 (Kras G12V) driven by ptf1a regulatory elements using a BAC recombineering strategy (Park et al., 2008). In this review, we describe the techniques that we used to observe the effects of eGFP-Kras G12V expression in pancreatic progenitor cells of the zebrafish embryo, as well as techniques used to characterize malignant pancreatic tumors in the adult zebrafish. This zebrafish model of pancreatic neoplasia provides a unique view of the effects of oncogenic Kras in the embryonic pancreas and suggests that the zebrafish will be a useful model organism in which to study the biology of Kras-initiated pancreatic neoplasia.
Davison
Jon M
JM
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Woo Park
Seung
S
Rhee
Jerry M
JM
Leach
Steven D
SD
D000818:Animals; D030801:Animals, Genetically Modified; D002454:Cell Differentiation / Q000187:drug effects; D022202:Chromosomes, Artificial, Bacterial; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D046790:Pancreas, Exocrine / Q000196:embryology / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016372:RNA, Antisense / Q000378:metabolism; D015027:Zebrafish; D018631:ras Proteins / Q000009:adverse effects* / Q000235:genetics*
D016372:RNA, Antisense; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D018631:ras Proteins