PUBLICATION

Inducible Intestine-Specific Expression of krasV12 Triggers Intestinal Tumorigenesis In Transgenic Zebrafish.

Authors
Lu, J.W., Raghuram, D., Fong, P.A., Gong, Z.
ID
ZDB-PUB-181106-9
Date
2018
Source
Neoplasia (New York, N.Y.)   20: 1187-1197 (Journal)
Registered Authors
Gong, Zhiyuan, Lu, Jeng-Wei
Keywords
none
MeSH Terms
  • Mutation
  • Gene Order
  • Genetic Vectors/genetics
  • Gene Expression*
  • Signal Transduction
  • Disease Models, Animal
  • Intestinal Mucosa/metabolism*
  • Intestinal Mucosa/pathology
  • Animals
  • Phosphorylation
  • Animals, Genetically Modified
  • DNA Transposable Elements
  • Proto-Oncogene Proteins p21(ras)/genetics*
  • Cell Transformation, Neoplastic/genetics*
  • Cell Transformation, Neoplastic/metabolism
  • Zebrafish
  • Cell Proliferation
  • Biomarkers
  • Genes, Reporter
(all 19)
PubMed
30390498 Full text @ Neoplasia
Abstract
KRAS mutations are a major risk factor in colorectal cancers. In particular, a point mutation of KRAS of amino acid 12, such as KRASV12, renders it stable activity in oncogenesis. We found that krasV12 promotes intestinal carcinogenesis by generating a transgenic zebrafish line with inducible krasV12 expression in the intestine, Tg(ifabp:EGFP-krasV12). The transgenic fish generated exhibited significant increases in the rates of intestinal epithelial outgrowth, proliferation, and cross talk in the active Ras signaling pathway involving in epithelial-mesenchymal transition (EMT). These results provide in vivo evidence of Ras pathway activation via krasV12 overexpression. Long-term transgenic expression of krasV12 resulted in enteritis, epithelial hyperplasia, and tubular adenoma in adult fish. This was accompanied by increased levels of the signaling proteins p-Erk and p-Akt and by downregulation of the EMT marker E-cadherin. Furthermore, we also observed a synergistic effect of krasV12 expression and dextran sodium sulfate treatment to enhance intestinal tumor in zebrafish. Our results demonstrate that krasV12 overexpression induces intestinal tumorigenesis in zebrafish, which mimics intestinal tumor formation in humans. Thus, our transgenic zebrafish may provide a valuable in vivo platform that can be used to investigate tumor initiation and anticancer drugs for gastrointestinal cancers.
Genes / Markers
Figures
Figure Gallery (5 images)
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Expression
Phenotype
No data available
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
gz37TgTransgenic Insertion
    1 - 1 of 1
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    Human Disease / Model
    No data available
    Sequence Targeting Reagents
    No data available
    Fish
    No data available
    Antibodies
    Orthology
    No data available
    Engineered Foreign Genes
    Marker Marker Type Name
    EGFPEFGEGFP
    1 - 1 of 1
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    Mapping
    No data available
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    Citation
    Lu, J.W., Raghuram, D., Fong, P.A., Gong, Z. (2018) Inducible Intestine-Specific Expression of krasV12 Triggers Intestinal Tumorigenesis In Transgenic Zebrafish.. Neoplasia (New York, N.Y.). 20:1187-1197.