Beta-catenin forms complexes with Tcf and Lef-1 and functions as a transcriptional activator in the Wnt signalling pathway. Although recent investigations have been focused on the role of the
adenomatous polyposis coli (APC)/
beta-catenin/Tcf pathway in human
tumorigenesis, there have been very few reports on mutations of the
beta-catenin gene in a variety of tumour types. Using PCR and single-strand conformational polymorphism analysis, we examined 93 lung, 9 breast, 6 kidney, 19 cervical and 7 ovarian
carcinoma cell lines for mutations in exon 3 of the
beta-catenin gene. In addition, we tested these same samples for mutations in the NH2-terminal regulatory region of the
gamma-catenin gene. Mutational analysis for the entire coding region of
beta-catenin cDNA was also undertaken in 20 lung, 9 breast, 5 kidney and 6 cervical
carcinoma cell lines. Deletion of most
beta-catenin coding exons was confirmed in line NCI-H28 (lung
mesothelioma) and a silent mutation at
codon 214 in exon 5 was found in HeLa (cervical
adenocarcinoma). A missense mutation at
codon 19 and a silent mutation at
codon 28 in the NH2-terminal regulatory region of the
gamma-catenin gene were found in H1726 (squamous cell lung
carcinoma) and H1048 (
small cell lung carcinoma), respectively. Neither deletions nor mutations of these genes were detected in the other cell lines examined. These results suggest that beta- and gamma-
catenins are infrequent mutational targets during development of human lung, breast, kidney, cervical and ovarian
carcinomas.