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Alterations of E-cadherin and β-catenin in gastric cancer

BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumou...

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Autores principales: Huiping, Chen, Kristjansdottir, Sigrun, Jonasson, Jon G, Magnusson, Jonas, Egilsson, Valgardur, Ingvarsson, Sigurdur
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2001
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC60969/
https://www.ncbi.nlm.nih.gov/pubmed/11747475
http://dx.doi.org/10.1186/1471-2407-1-16
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author Huiping, Chen
Kristjansdottir, Sigrun
Jonasson, Jon G
Magnusson, Jonas
Egilsson, Valgardur
Ingvarsson, Sigurdur
author_facet Huiping, Chen
Kristjansdottir, Sigrun
Jonasson, Jon G
Magnusson, Jonas
Egilsson, Valgardur
Ingvarsson, Sigurdur
author_sort Huiping, Chen
collection PubMed
description BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. METHODS: We studied the alterations of E-cadherin and β-catenin in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC). RESULTS: A high frequency (75%) of LOH was detected at 16q22.1 containing E-cadherin locus. Three cases (6%) showed the identical missense mutation, A592T. This mutation is not likely to contribute strongly to the carcinogenesis of gastric cancer, because a low frequency (1.6%) of this mutation was also found in 187 normal individuals. We also detected a low frequency (0.36%, 0%) of this mutation in 280 breast tumours and 444 other tumours, including colon and rectum, lung, endometrium, ovary, testis, kidney, thyroid carcinomas and sarcomas, respectively. We also analyzed the aberrant E-cadherin mRNAs in the gastric tumours and found that 7 tumours (18%) had aberrant mRNAs in addition to the normal mRNA. These aberrant mRNAs may produce abnormal E-cadherin molecules, resulting in weak cell-cell adhesion and invasive behaviour of carcinoma cells. Reduced expression of E-cadherin and β-catenin was identified at the frequency of 42% and 28%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for β-catenin IHC. An association was found between reduced expression of E-cadherin and β-catenin. Moreover, an association was detected between reduced expression of E-cadherin and diffuse histotype. CONCLUSION: Our results support the hypothesis that alterations of E-cadherin and β-catenin play a role in the initiation and progression of gastric cancer.
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spelling pubmed-609692001-12-13 Alterations of E-cadherin and β-catenin in gastric cancer Huiping, Chen Kristjansdottir, Sigrun Jonasson, Jon G Magnusson, Jonas Egilsson, Valgardur Ingvarsson, Sigurdur BMC Cancer Research Article BACKGROUND: The E-cadherin-catenin complex plays a crucial role in epithelial cell-cell adhesion and in the maintenance of tissue architecture. Perturbation in the expression or function of this complex results in loss of intercellular adhesion, with possible consequent cell transformation and tumour progression. METHODS: We studied the alterations of E-cadherin and β-catenin in a set of 50 primary gastric tumours by using loss of heterozygosity (LOH) analysis, gene mutation screening, detection of aberrant transcripts and immunohistochemistry (IHC). RESULTS: A high frequency (75%) of LOH was detected at 16q22.1 containing E-cadherin locus. Three cases (6%) showed the identical missense mutation, A592T. This mutation is not likely to contribute strongly to the carcinogenesis of gastric cancer, because a low frequency (1.6%) of this mutation was also found in 187 normal individuals. We also detected a low frequency (0.36%, 0%) of this mutation in 280 breast tumours and 444 other tumours, including colon and rectum, lung, endometrium, ovary, testis, kidney, thyroid carcinomas and sarcomas, respectively. We also analyzed the aberrant E-cadherin mRNAs in the gastric tumours and found that 7 tumours (18%) had aberrant mRNAs in addition to the normal mRNA. These aberrant mRNAs may produce abnormal E-cadherin molecules, resulting in weak cell-cell adhesion and invasive behaviour of carcinoma cells. Reduced expression of E-cadherin and β-catenin was identified at the frequency of 42% and 28%, respectively. Specially, 11 tumours (22%) exhibited positive cytoplasmic staining for β-catenin IHC. An association was found between reduced expression of E-cadherin and β-catenin. Moreover, an association was detected between reduced expression of E-cadherin and diffuse histotype. CONCLUSION: Our results support the hypothesis that alterations of E-cadherin and β-catenin play a role in the initiation and progression of gastric cancer. BioMed Central 2001-10-29 /pmc/articles/PMC60969/ /pubmed/11747475 http://dx.doi.org/10.1186/1471-2407-1-16 Text en Copyright © 2001 Huiping et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research Article
Huiping, Chen
Kristjansdottir, Sigrun
Jonasson, Jon G
Magnusson, Jonas
Egilsson, Valgardur
Ingvarsson, Sigurdur
Alterations of E-cadherin and β-catenin in gastric cancer
title Alterations of E-cadherin and β-catenin in gastric cancer
title_full Alterations of E-cadherin and β-catenin in gastric cancer
title_fullStr Alterations of E-cadherin and β-catenin in gastric cancer
title_full_unstemmed Alterations of E-cadherin and β-catenin in gastric cancer
title_short Alterations of E-cadherin and β-catenin in gastric cancer
title_sort alterations of e-cadherin and β-catenin in gastric cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC60969/
https://www.ncbi.nlm.nih.gov/pubmed/11747475
http://dx.doi.org/10.1186/1471-2407-1-16
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