title: Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia.
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.
authors.affiliation: Hubrecht Laboratorium, NIOB/KNAW, Center for Biomedical Genetics, CT Utrecht, The Netherlands.
authors.forename: Anna-Pavlina G
authors.initials: AP
authors.lastname: Haramis
authors.forename: Adam
authors.initials: A
authors.lastname: Hurlstone
authors.forename: Yme
authors.initials: Y
authors.lastname: van der Velden
authors.forename: Harry
authors.initials: H
authors.lastname: Begthel
authors.forename: Maaike
authors.initials: M
authors.lastname: van den Born
authors.forename: G Johan A
authors.initials: GJ
authors.lastname: Offerhaus
authors.forename: Hans C
authors.initials: HC
authors.lastname: Clevers
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D025601:Adenomatous Polyposis Coli Protein / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D030801:Animals, Genetically Modified; D004067:Digestive System Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000662:veterinary; D015972:Gene Expression Regulation, Neoplastic; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*
chemical_list: D025601:Adenomatous Polyposis Coli Protein