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Kremer, M. ; Quintanilla-Martinez, L. ; Fuchs, M.* ; Gamboa-Dominguez, A.* ; Haye, S.* ; Kalthoff, H.* ; Rosivatz, E.* ; Hermannstädter, C.* ; Busch, R.* ; Höfler, H. ; Luber, B.*

Influence of tumor-associated E-cadherin mutations on tumorgenicity and metastasis.

Carcinogenesis 24, 1879-1886 (2003)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Language english
Publication Year 2003
HGF-reported in Year 0
ISSN (print) / ISBN 0143-3334
e-ISSN 1460-2180
Journal Carcinogenesis
Quellenangaben Volume: 24, Issue: 12, Pages: 1879-1886 Article Number: , Supplement: ,
Publisher Oxford University Press
Reviewing status Peer reviewed
POF-Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-500300-001
Erfassungsdatum 2003-12-12