APC truncation and increased beta-catenin levels in a human breast cancer cell line.
Mutations in the Adenomatous Polyposis Coli (APC) tumor suppressor gene or the beta-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 beta- and gamma-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 beta-catenin levels, probably due to loss of APC function, as in colon cancers. No mutations were found in exon 3 of the beta- or gamma-catenin genes. We conclude that APC mutations and beta-catenin upregulation may occur with low frequency in human breast cancer cells.
Schlosshauer
P W
PW
Department of Pathology, Columbia University, College of Physicians and Surgeons, 630 West 168th Street, New York, NY 10032, USA.
Brown
S A
SA
Eisinger
K
K
Yan
Q
Q
Guglielminetti
E R
ER
Parsons
R
R
Ellenson
L H
LH
Kitajewski
J
J
D025601:Adenomatous Polyposis Coli Protein; D015153:Blotting, Western; D001940:Breast / Q000166:cytology; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D002461:Cell Line, Transformed; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D051180:Desmoplakins; D017491:Genes, APC / Q000235:genetics*; D006801:Humans; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014407:Tumor Cells, Cultured; D051176:beta Catenin; D051185:gamma Catenin
D025601:Adenomatous Polyposis Coli Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D051180:Desmoplakins; C495292:JUP protein, human; D015534:Trans-Activators; D051176:beta Catenin; D051185:gamma Catenin