Oncogenic KRAS Induces Progenitor Cell Expansion and Malignant Transformation in Zebrafish Exocrine Pancreas

Park, Seung Woo; Davison, Jon M.; Rhee, Jerry M.; Hruban, Ralph H.; Maitra, Anirban; Leach, Steven D.

doi:10.1053/j.gastro.2008.02.084

Cited by 134 publications

(128 citation statements)

References 29 publications

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“…Homologous recombination leads to accurate replacement of the Ptf1a coding sequences with the eGFP and eGFP-Kras transgene (Davison, Woo Park et al 2008). Their results demonstrate that oncogenic Kras-expressed pancreatic progenitor cells fail to undergo characteristic exocrine differentiation although their initial specification and migration are observed to be normal (Davison, Woo Park et al 2008;Park, Davison et al 2008). Blocks of differentiation leads to abnormal accumulation of the undifferentiated progenitor cells, correlates with the formation of invasive pancreatic cancer.…”

Section: Studies Of Kras-mediated Pancreatic Tumorigenesis With Bacsmentioning

confidence: 99%

“…The studies have also shown that mammalian and zebrafish pancreas are significantly similar in anatomy and histology (Wallace and Pack 2003;Chen, Li et al 2007). Therefore, the Zebrafish has emerged as an experimental model for study of human pancreatic cancer biology (Davison, Woo Park et al 2008;Park, Davison et al 2008). Another benefits of working with zebrafish model is their translucency, which greatly improves the visualization of fluorescent trangenes in both embryos and adult zebrafish (Davison, Woo Park et al 2008).…”

Section: Studies Of Kras-mediated Pancreatic Tumorigenesis With Bacsmentioning

confidence: 99%

See 1 more Smart Citation

Gene Functional Studies Using Bacterial Artificial Chromosome (BACs)

Liu¹,

Guo²,

Battle³

et al. 2011

Bacterial Artificial Chromosomes

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Section: Studies Of Kras-mediated Pancreatic Tumorigenesis With Bacsmentioning

confidence: 99%

Section: Studies Of Kras-mediated Pancreatic Tumorigenesis With Bacsmentioning

confidence: 99%

Gene Functional Studies Using Bacterial Artificial Chromosome (BACs)

Liu¹,

Guo²,

Battle³

et al. 2011

Bacterial Artificial Chromosomes

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“…Using a transgenic reporter line of zebrafish that express GFP under the control of the ela3I (elastase A) promoter, research from the Lin lab has studied the effects of retinoids on exocrine pancreas development . Using pancreasspecific promoters it has been possible to create models of both exocrine and endocrine pancreatic tumors (Yang et al 2004, Park et al 2008. It is possible to envision chemical screens using zebrafish embryos to identify compounds capable of promoting b-cell differentiation, or compounds blocking early stages of transformation in tumor models.…”

Section: Pancreasmentioning

confidence: 99%

“…www.endocrinology-journals.org development (Park et al 2008). By directly observing pancreatic progenitor cells during development, they were able to demonstrate that KRAS G12V expression induces a block in differentiation of exocrine progenitors.…”

Section: Pancreatic Cancermentioning

confidence: 99%

Hooked on zebrafish: insights into development and cancer of endocrine tissues

Bourque¹,

Houvras²

2011

Endocrine-Related Cancer

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Zebrafish is emerging as a unique model organism for studying cancer genetics and biology. For several decades zebrafish have been used to study vertebrate development, where they have made important contributions to understanding the specification and differentiation programs in many tissues. Recently, zebrafish studies have led to important insights into thyroid development, and have been used to model endocrine cancer. Zebrafish possess a unique set of attributes that make them amenable to forward and reverse genetic approaches. Zebrafish embryos develop rapidly and can be used to study specific cell lineages or the effects of chemicals on pathways or tissue development. In this review, we highlight the structure and function of endocrine organs in zebrafish and outline the major achievements in modeling cancer. Our goal is to familiarize readers with the zebrafish as a genetic model system and propose opportunities for endocrine cancer research in zebrafish.

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“…Recent comparative genomics analysis of the zebrafish reference genome (Zv9) revealed 26,206 protein-coding genes, with 71% having human orthologues, of which 82% are correlated with diseaseassociated genes in the Online Mendelian Inheritance in Man (OMIM) database 13,14 . Consequently, the zebrafish has been used to model diverse types of human cancers, including neuroblastoma 8 , T-cell acute lymphoblastic leukemia (T-ALL) 15,16 , melanoma 17,18 , Ewing's sarcoma 19 , rhabdomyosarcoma 20,21 , pancreatic carcinoma 22 , hepatocellular carcinoma 23 and myeloid malignancies 24,25 , and has been selected as a cancer model for xenotransplantation studies . To develop such a model ( Figure 1A), one injects a DNA construct containing the gene of interest driven by a tissue-specific promoter into one-cell wild-type embryos.…”

Section: Introductionmentioning

confidence: 99%

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

Ung

Guo

Zhu

et al. 2015

JoVE

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Comprehensive genomic analysis has uncovered surprisingly large numbers of genetic alterations in various types of cancers. To robustly and efficiently identify oncogenic "drivers" among these tumors and define their complex relationships with concurrent genetic alterations during tumor pathogenesis remains a daunting task. Recently, zebrafish have emerged as an important animal model for studying human diseases, largely because of their ease of maintenance, high fecundity, obvious advantages for in vivo imaging, high conservation of oncogenes and their molecular pathways, susceptibility to tumorigenesis and, most importantly, the availability of transgenic techniques suitable for use in the fish. Transgenic zebrafish models of cancer have been widely used to dissect oncogenic pathways in diverse tumor types. However, developing a stable transgenic fish model is both tedious and time-consuming, and it is even more difficult and more time-consuming to dissect the cooperation of multiple genes in disease pathogenesis using this approach, which requires the generation of multiple transgenic lines with overexpression of the individual genes of interest followed by complicated breeding of these stable transgenic lines. Hence, use of a mosaic transient transgenic approach in zebrafish offers unique advantages for functional genomic analysis in vivo. Briefly, candidate transgenes can be coinjected into one-cell-stage wild-type or transgenic zebrafish embryos and allowed to integrate together into each somatic cell in a mosaic pattern that leads to mixed genotypes in the same primarily injected animal. This permits one to investigate in a faster and less expensive manner whether and how the candidate genes can collaborate with each other to drive tumorigenesis. By transient overexpression of activated ALK in the transgenic fish overexpressing MYCN, we demonstrate here the cooperation of these two oncogenes in the pathogenesis of a pediatric cancer, neuroblastoma that has resisted most forms of contemporary treatment. Video LinkThe video component of this article can be found at

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Oncogenic KRAS Induces Progenitor Cell Expansion and Malignant Transformation in Zebrafish Exocrine Pancreas

Cited by 134 publications

References 29 publications

Gene Functional Studies Using Bacterial Artificial Chromosome (BACs)

Gene Functional Studies Using Bacterial Artificial Chromosome (BACs)

Hooked on zebrafish: insights into development and cancer of endocrine tissues

Mosaic Zebrafish Transgenesis for Functional Genomic Analysis of Candidate Cooperative Genes in Tumor Pathogenesis

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