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

TY - JOUR

T1 - Adenomatous polyposis coli-deficient zebrafish are susceptible to digestive tract neoplasia.

AU - Haramis, A.-P.G.

AU - Hurlstone, A.

AU - Velden, Y. van der

AU - Begthel, H.

AU - Born, M. van den

AU - Offerhaus, G.J.A.

AU - Clevers, J.C.

N1 - doi: 10.1038/sj.embor.7400638. PMC_URL: http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1456916&blobtype=pdf

PY - 2006

Y1 - 2006

N2 - 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.

AB - 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.

M3 - Article

SN - 1469-221X

VL - 7

SP - 444

EP - 449

JO - EMBO Reports

JF - EMBO Reports

ER -