論文 - 詳細
| RRC ID | 72297 |
|---|---|
| 著者 | van de Wetering M, Barker N, Harkes IC, van der Heyden M, Dijk NJ, Hollestelle A, Klijn JG, Clevers H, Schutte M. |
| タイトル | Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling. |
| ジャーナル | Cancer Res |
| Abstract |
Participation of E-cadherin in the Wnt signaling pathway was suggested because of the dual role of beta-catenin in cell adhesion and the Wnt signaling cascade. Whereas beta-catenin interacts at the cell membrane with the cell adhesion protein E-cadherin, in the nucleus it activates Wnt target genes through formation of transcriptionally active complexes with members of the Tcf/Lef family of transcription factors. Here, we analyzed by PCR and direct cycle sequencing 26 human breast cancer cell lines for alterations in the E-cadherin gene. Genetic alterations were identified in eight cell lines. Five cell lines had truncating mutations, whereas three cell lines had in-frame deletions in the gene transcript and expressed mutant E-cadherin proteins at the cell membrane. Involvement of E-cadherin in the Wnt pathway was evaluated through determination of the activity of a Tcf reporter gene, which had been transiently transfected into 15 breast cancer cell lines. None of six E-cadherin mutant cell lines and four cell lines that exhibit transcriptional silencing of the E-cadherin gene showed Tcf-mediated transcriptional activation. E-cadherin wild-type cell line DU4475 exhibited constitutive Tcf-beta-catenin signaling activity and was found to express truncated APC proteins. These results indicate that if cellular transformation occurred through mutation of E-cadherin, it is not mediated via constitutive activation of the Wnt signaling pathway. |
| 巻・号 | 61(1) |
| ページ | 278-84 |
| 公開日 | 2001-1-1 |
| PMID | 11196175 |
| MeSH | Breast Neoplasms / genetics* Breast Neoplasms / metabolism Cadherins / biosynthesis Cadherins / genetics* DNA Mutational Analysis DNA-Binding Proteins / genetics Gene Expression Gene Silencing Genes, Reporter Humans Luciferases / genetics Lymphoid Enhancer-Binding Factor 1 Mutation Proto-Oncogene Proteins / physiology* Signal Transduction / physiology* Transcription Factors / genetics Transcriptional Activation / physiology Tumor Cells, Cultured Wnt Proteins Zebrafish Proteins* |
| IF | 9.727 |
| 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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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 12 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 3.0 |
| リソース情報 | |
| ヒト・動物細胞 | OCUB-F(RCB0882) |