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.
Citation
Haramis, A.P., Hurlstone, A., van der Velden, Y., Begthel, H., van den Born, M., Offerhaus, G.J., and Clevers, H.C. (2006) Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia. EMBO reports. 7(4):444-449.
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
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping