Journal Article

Influence of tumor-associated E-cadherin mutations on tumorigenicity and metastasis

Marcus Kremer, Leticia Quintanilla-Martinez, Margit Fuchs, Armando Gamboa-Dominguez, Sieglinde Haye, Holger Kalthoff, Erika Rosivatz, Christine Hermannstädter, Raymonde Busch, Heinz Höfler and Birgit Luber

in Carcinogenesis

Volume 24, issue 12, pages 1879-1886
Published in print December 2003 | ISSN: 0143-3334
Published online December 2003 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgg148
Influence of tumor-associated E-cadherin mutations on tumorigenicity and metastasis

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In this study, we investigated whether tumor-associated E-cadherin mutations impair the tumor-suppressive function of the cell adhesion molecule and influence metastasis formation in a severe combined immunodeficiency mouse model. The investigated E-cadherin mutations were in frame deletions of exons 8 (del 8) or 9 (del 9) and a point mutation in exon 8 (p8). Transfected human MDA-MB-435S carcinoma cells stably expressing wild-type (wt) or mutant E-cadherin were injected into the mouse mammary fat pad. Mice transplanted with wt E-cadherin transfectants developed significantly smaller tumors than animals transplanted with the E-cadherin-negative parental cell line. Animals transplanted with del 9 or p8 E-cadherin transfectants produced medium size tumors, indicating that these mutations impair the tumor-suppressive function of E-cadherin. In contrast, mice transplanted with del 8 E-cadherin transfectants developed tumors of approximately the same sizes as animals transplanted with wt E-cadherin expressing cells. Lung metastases were induced by all cell lines without significant differences. Immunohistochemical analysis of E-cadherin expression in the tumors revealed a heterogeneous staining pattern, indicating loss or down-regulation of E-cadherin in some tumor cells. Metastases were completely negative for E-cadherin. Our data suggest that the type of mutation determines whether the tumor-suppressive function of E-cadherin is impaired.

Keywords: del 8 E-cadherin, E-cadherin with deletion of exon 8; del 9 E-cadherin, E-cadherin with deletion of exon 9; p8 E-cadherin, E-cadherin with point mutation in exon 8; SCID, severe combined immunodeficiency; wt E-cadherin, wild-type E-cadherin

Journal Article.  5029 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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