Koyama Toru, Tago Ken-Ichi, Nakamura Tsutomu, Ohwada Susumu, Morishita Yasuo, Yokota Jun, Akiyama Tetsu
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.
Jpn J Clin Oncol. 2002 Sep;32(9):358-62. doi: 10.1093/jjco/hyf068.
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.
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.
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.
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.
