Mutation and expression of the beta-catenin-interacting protein ICAT in human colorectal tumors.
BACKGROUND
Aberrant activation of Wnt signaling caused by mutations in the tumor suppressor adenomatous polyposis coli or beta-catenin is a critical event in the development of human colorectal tumors. We have recently identified the ICAT gene, which encodes a small protein that interacts with beta-catenin and represses Wnt signaling.


METHODS
We examined the prevalence of mutations in the entire ICAT coding sequence and intronic splice donor and acceptor regions of ICAT by PCR-SSCP and also the expression of the ICAT gene by RT-PCR.


RESULTS
The ICAT gene was mapped to chromosome 1p36.1-p36.2, which is implicated in the pathogenesis of various types of cancers. However, no mutations in ICAT were detected among 128 colorectal tumors. Instead, ICAT was found to be overexpressed in almost half of colorectal carcinomas. Cases exhibiting ICAT overexpression showed a significantly higher incidence of well-differentiated adenocarcinoma and positive lymphatic permeation.


CONCLUSIONS
Our results suggest that ICAT is not the putative tumor suppressor on 1p36.1-p36.2, although aberrant overexpression of ICAT may play a role in the pathogenesis of colorectal carcinomas.
Koyama
Toru
T
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Laboratory of Molecular and Genetic Information, Institution of Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
Tago
Ken-Ichi
K
Nakamura
Tsutomu
T
Ohwada
Susumu
S
Morishita
Yasuo
Y
Yokota
Jun
J
Akiyama
Tetsu
T
D048868:Adaptor Proteins, Signal Transducing; D011125:Adenomatous Polyposis Coli / Q000235:genetics; D000368:Aged; D018797:Cell Cycle Proteins; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017491:Genes, APC; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D012004:Rectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000096:biosynthesis*; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495270:CTNNB1 protein, human; C411982:CTNNBIP1 protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin