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- Rask, Katarina, 1966, et al.
(author)
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Wnt-signalling pathway in ovarian epithelial tumours: increased expression of beta-catenin and GSK3 beta
- 2003
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In: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 89:7, s. 1298-1304
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Journal article (peer-reviewed)abstract
- Beta-catenin is involved in both cell-cell adhesion and in transcriptional regulation by the Wingless/Wnt signalling pathway. Alterations of components of this pathway have been suggested to play a central role in tumorigenesis. The present study investigated, by immunohistochemistry and immunoblotting, the protein expression and localisation of beta-catenin, adenomatous polyposis coli (APC), glycogen synthase kinase 3beta (GSK3beta) and lymphocyte enhancer factor-1 (Lef-1) in normal human ovaries and in epithelial ovarian tumours in vivo and in vitro. Immortalised human ovarian surface epithelium and ovarian cancer cell cells (OVCAR-3) expressed beta-catenin, APC, GSK3beta and Lef-1. Nuclear staining of beta-catenin and Lef-1 were demonstrated only in OVCAR-3 cells. There were significant increases of beta-catenin and GSK3beta, while APC was reduced in ovarian cancer compared to the normal ovary. Beta-catenin and Lef-1 were coimmunoprecipitated in ovarian tumours, but not in the normal ovary. Nuclear localisation of beta-catenin or Lef-1 could not be demonstrated in the normal ovary or in the ovarian tumours. The absence of nuclear localisation of beta-catenin could be due to an increased binding to the cadherin-alpha-catenin cell adhesion complex. In fact, we have earlier reported an increased expression of E-cadherin in ovarian adenocarcinomas. In summary, this study demonstrates an increase in the expression of components of the Wingless/Wnt pathway in malignant ovarian tumours. The increase suggests a role for this signalling pathway in cell transformation and in tumour progression. However, it remains to be demonstrated whether it is an increased participation of beta-catenin in transcriptional regulation, or in the stabilisation of cellular integrity, or both, that is the crucial event in ovarian tumorigenesis.
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