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. 2001 Jan 1;61(1):278-84.

Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling

M van de Wetering  1 , N Barker, I C Harkes, M van der Heyden, N J Dijk, A Hollestelle, J G Klijn, H Clevers, M Schutte
Affiliations
  • PMID: 11196175

Mutant E-cadherin breast cancer cells do not display constitutive Wnt signaling

M van de Wetering et al. 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.

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