Overexpression of Wnt target genes in adenomas of familial adenomatous polyposis patients.
Germline mutations within the adenomatous polyposis coli (APC) gene, a key member of the Wnt signalling pathway, have been shown to cause adenoma development in familial adenomatous polyposis (FAP), a dominantly inherited predisposition to colorectal cancer. Although it has been suggested for several years that alterations within the Wnt pathway are the underlying events for the development of colorectal adenomas in FAP patients, no detailed analysis of the gene expressions of Wnt pathway members has been available in fresh colorectal tissue of FAP patients, so far. Thus, we investigated potential differences in the expressions of APC and its Wnt partners conductin, beta-catenin, cyclin D1, and c-myc in normal colorectal mucosa and matched adenoma tissue of 14 FAP patients using real-time quantitative PCR. The expressions of both Wnt target genes, cyclin D1 and c-myc, were significantly increased in adenoma compared to matched normal mucosa. Furthermore, the overexpressions of these two genes showed a highly significant positive correlation. Our data suggest that the concomitant overexpression of the Wnt targets and cell cycle regulators cyclin D1 and c-myc plays an important role in the neoplastic proliferation of adenomas in FAP patients.
D'Orazio
Daniel
D
Research Group Human Genetics, Division of Medical Genetics, Department of Clinical-Biological Sciences, University of Basel, CH-4031, Switzerland.
Muller
Patrick Y
PY
Heinimann
Karl
K
Albrecht
Christiane
C
Bendik
Igor
I
Herzog
Urs
U
Tondelli
Peter
P
Bauerfeind
Peter
P
Müller
Hansjakob
H
Dobbie
Zuzana
Z
D011125:Adenomatous Polyposis Coli / Q000235:genetics* / Q000378:metabolism; D025601:Adenomatous Polyposis Coli Protein / Q000096:biosynthesis / Q000235:genetics; D000293:Adolescent; D000328:Adult; D060466:Axin Protein; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
C491761:AXIN2 protein, human; D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D015534:Trans-Activators; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin; D019938:Cyclin D1