APC truncation and increased β-catenin levels in a human breast cancer cell line

Abstract

Mutations in the Adenomatous Polyposis Coli ( APC ) tumor suppressor gene or the β- catenin gene are present in most colon cancers and less frequently in other tumor types. In this study, we screened 24 human breast cancer cell lines and three immortalized human breast epithelial cell lines for alterations in β- and γ-catenin and APC by western blotting, protein truncation assay and DNA sequence analysis. In one cell line (DU 4475), an APC mutation was identified (E1577stop) that resulted in expression of truncated APC. This mutation was associated with elevated cytosolic β-catenin levels, probably due to loss of APC function, as in colon cancers. No mutations were found in exon 3 of the β- or γ- catenin genes. We conclude that APC mutations and β-catenin upregulation may occur with low frequency in human breast cancer cells.