Seung Woo Park

Publications (2)13.72 Total impact

• Article: Oncogenic KRAS induces progenitor cell expansion and malignant transformation in zebrafish exocrine pancreas.

  Seung Woo Park, Jon M Davison, Jerry Rhee, Ralph H Hruban, Anirban Maitra, Steven D Leach
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  ABSTRACT: Although the cell of origin for pancreatic cancer remains unknown, prior studies have suggested that pancreatic neoplasia may be initiated in progenitor-like cells. To examine the effects of oncogene activation within the pancreatic progenitor pool, we devised a system for real-time visualization of both normal and oncogenic KRAS-expressing pancreatic progenitor cells in living zebrafish embryos. By using BAC transgenes under the regulation of ptf1a regulatory elements, we expressed either extended green fluorescent protein (eGFP) alone or eGFP fused to oncogenic KRAS in developing zebrafish pancreas. After their initial specification, normal eGFP-labeled pancreatic progenitor cells were observed to actively migrate away from the forming endodermal gut tube, and subsequently underwent characteristic exocrine differentiation. In contrast, pancreatic progenitor cells expressing oncogenic KRAS underwent normal specification and migration, but failed to differentiate. This block in differentiation resulted in the abnormal persistence of an undifferentiated progenitor pool, and was associated with the subsequent formation of invasive pancreatic cancer. These tumors showed several features in common with the human disease, including evidence of abnormal Hedgehog pathway activation. These results provide a unique view of the tumor-initiating effects of oncogenic KRAS in a living vertebrate organism, and suggest that zebrafish models of pancreatic cancer may prove useful in advancing our understanding of the human disease.
  Gastroenterology 06/2008; 134(7):2080-90. · 11.68 Impact Factor
• Article: Characterization of Kras-mediated pancreatic tumorigenesis in zebrafish.

  Jon M Davison, Seung Woo Park, Jerry M Rhee, Steven D Leach
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  ABSTRACT: 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.
  Methods in Enzymology 02/2008; 438:391-417. · 2.04 Impact Factor