| RRC ID |
18890
|
| 著者 |
Hollestelle A, Elstrodt F, Timmermans M, Sieuwerts AM, Klijn JG, Foekens JA, den Bakker MA, Schutte M.
|
| タイトル |
Four human breast cancer cell lines with biallelic inactivating alpha-catenin gene mutations.
|
| ジャーナル |
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.
|
| 巻・号 |
122(1)
|
| ページ |
125-33
|
| 公開日 |
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
|
| 引用数 |
25
|
|
WOS 分野
|
ONCOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
OCUB-F(RCB0882)
OCUB-M(RCB0881) |
