| 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
|
| リソース情報 |
| ヒト・動物細胞 |
OCUB-F(RCB0882) |
