RRC ID 18890
Author Hollestelle A, Elstrodt F, Timmermans M, Sieuwerts AM, Klijn JG, Foekens JA, den Bakker MA, Schutte M.
Title Four human breast cancer cell lines with biallelic inactivating alpha-catenin gene mutations.
Journal Breast Cancer Res Treat
Abstract Mutations of E-cadherin have been identified in half of lobular breast cancers and diffuse-type gastric cancers, two tumor subtypes with remarkably similar pathological appearances including small rounded cells with scant cytoplasm and a diffuse growth pattern. A causal role for E-cadherin gene mutations in the lobular breast cancer phenotype was recently demonstrated in E-cadherin knock-out mice. These observations suggested that another gene in the E-cadherin tumor suppressor pathway might be mutated in lobular breast cancers with wild-type E-cadherin genes. Here, we identified E-cadherin gene mutations exclusively in human breast cancer cell lines that grow with a rounded cell morphology. Using expression analyses and gene mutation analyses, we have identified four biallelic inactivating alpha-catenin mutations among 55 human breast cancer cell lines. All four alpha-catenin mutations predicted premature termination of the encoded proteins, and concordantly, none of the four mutant cell lines expressed alpha-catenin proteins. Importantly, three of the alpha-catenin mutant cell lines had the rounded cell morphology and all 14 cell lines with the rounded cell morphology had mutations of either E-cadherin or alpha-catenin. As anticipated, loss of alpha-catenin protein expression was associated with the lobular subtype in primary breast cancers. Together, our observations suggest that alpha-catenin may be a new tumor suppressor gene that operates in the E-cadherin tumor suppressor pathway.
Volume 122(1)
Pages 125-33
Published 2010-7-1
DOI 10.1007/s10549-009-0545-4
PMID 19763817
MeSH Alleles Breast Neoplasms / genetics Breast Neoplasms / pathology* Cadherins / genetics Cadherins / physiology Carcinoma / genetics Carcinoma / pathology* Carcinoma, Lobular / genetics Carcinoma, Lobular / pathology Cell Adhesion / genetics Cell Line, Tumor / metabolism Cell Shape / genetics Codon, Nonsense* DNA Methylation Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genes, Tumor Suppressor* Humans Neoplasm Proteins / biosynthesis Neoplasm Proteins / deficiency Neoplasm Proteins / genetics* Oligonucleotide Array Sequence Analysis alpha Catenin / biosynthesis alpha Catenin / deficiency alpha Catenin / genetics*
IF 3.831
Times Cited 25
Human and Animal Cells OCUB-F(RCB0882) OCUB-M(RCB0881)