Format

Send to

Choose Destination
See comment in PubMed Commons below
Proc Natl Acad Sci U S A. 1997 Sep 16;94(19):10330-4.

Beta-catenin mutations in cell lines established from human colorectal cancers.

Author information

1
Cancer Genetics and Immunology Laboratory, Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom. ilyas@europa.lif.icnet.uk

Abstract

beta-catenin has functions as both an adhesion and a signaling molecule. Disruption of these functions through mutations of the beta-catenin gene (CTNNB1) may be important in the development of colorectal tumors. We examined the entire coding sequence of beta-catenin by reverse transcriptase-PCR (RT-PCR) and direct sequencing of 23 human colorectal cancer cell lines from 21 patients. In two cell lines, there was apparent instability of the beta-catenin mRNA. Five different mutations (26%) were found in the remaining 21cell lines (from 19 patients). A three-base deletion (codon 45) was identified in the cell line HCT 116, whereas cell lines SW 48, HCA 46, CACO 2, and Colo 201 each contained single-base missense mutations (codons 33, 183, 245, and 287, respectively). All 23 cell lines had full-length beta-catenin protein that was detectable by Western blotting and that coprecipitated with E-cadherin. In three of the cell lines with CTNNB1 mutations, complexes of beta-catenin with alpha-catenin and APC were detectable. In SW48 and HCA 46, however, we did not detect complexes of beta-catenin protein with alpha-catenin and APC, respectively. These results show that selection of CTNNB1 mutations occurs in up to 26% of colorectal cancers from which cell lines are derived. In these cases, mutation selection is probably for altered beta-catenin function, which may significantly alter intracellular signaling and intercellular adhesion and may serve as a complement to APC mutations in the early stages of tumorigenesis.

PMID:
9294210
PMCID:
PMC23362
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center