論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ヒト・動物細胞 | OCUB-F(RCB0882) OCUB-M(RCB0881) |