PUBLICATION

Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia

Authors
Haramis, A.P., Hurlstone, A., van der Velden, Y., Begthel, H., van den Born, M., Offerhaus, G.J., and Clevers, H.C.
ID
ZDB-PUB-060130-10
Date
2006
Source
EMBO reports   7(4): 444-449 (Journal)
Registered Authors
Clevers, Hans, Haramis, Anna-Pavlina
Keywords
none
MeSH Terms
  • Adenoma/genetics
  • Adenoma/metabolism*
  • Adenoma/pathology*
  • Adenomatous Polyposis Coli Protein/deficiency*
  • Adenomatous Polyposis Coli Protein/genetics
  • Adenomatous Polyposis Coli Protein/metabolism*
  • Animals
  • Animals, Genetically Modified
  • Digestive System Neoplasms/genetics
  • Digestive System Neoplasms/metabolism*
  • Digestive System Neoplasms/pathology*
  • Digestive System Neoplasms/veterinary
  • Gene Expression Regulation, Neoplastic
  • Zebrafish/genetics
  • Zebrafish/metabolism*
PubMed
16439994 Full text @ EMBO Rep.
Abstract
Truncation of the tumour suppressor adenomatous polyposis coli (APC) constitutively activates the Wnt/beta-catenin signalling pathway. This event constitutes the primary transforming event in sporadic colorectal cancer in humans. Moreover, humans or mice carrying germline truncating mutations in APC develop large numbers of intestinal adenomas. Here, we report that zebrafish that are heterozygous for a truncating APC mutation spontaneously develop intestinal, hepatic and pancreatic neoplasias that are highly proliferative, accumulate beta-catenin and express Wnt target genes. Treatment with the chemical carcinogen 7,12-dimethylbenz[a]anthracene accelerates the induction of these lesions. These observations establish apc-mutant zebrafish as a bona fide model for the study of digestive tract cancer.
Genes / Markers
Figures
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping