Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer

Matsui, Shigeo; Shiozaki, Hitoshi; Inoue, Masakí; Tamura, Shigeyuki; Doki, Yuichiro; Kadowaki, Takatoshi; Iwazawa, Takashi; Shimaya, K; Nagafuchi, Akira; Tsukita, Shöichiro

doi:10.1007/bf00190559

Cited by 99 publications

(82 citation statements)

References 32 publications

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“…A germline mutation in E-cadherin associated with familial gastric cancer was recently reported in a New Zealand kindred (Guilford et al, 1998). Mutations in α-and β-catenins have not been convincingly demonstrated, but protein expression abnormalities are relatively frequent, and occur in both diffuse and intestinal cancers (Oka et al, 1992;Matsui et al, 1994;Jawhari et al, 1997). We have confirmed a high frequency of expression abnormalities for all three molecules studied.…”

Section: Discussionsupporting

confidence: 62%

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

1999

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Summary β-catenin, a component of the E-cadherin-catenin cell adhesion complex, also plays a separate intracellular signalling role, interacting with APC protein. Intracellular accumulation of β-catenin is common in colorectal neoplasia. β-catenin abnormalities are associated with poor survival in gastric cancer, but previous studies do not differentiate between membrane-associated and intracellular β-catenin. In this study we aimed to determine which type of expression abnormalities for E-cadherin, β-catenin and α-catenin correlate with clinico-pathological features and survival in gastric cancer. Immunoperoxidase staining of paraffin-embedded sections from 40 gastric cancers was performed for E-cadherin, α-and β-catenins using microwave unmasking and an avidin-biotin technique. Clinical data were obtained from case records and cancer registry records. Reduced membranous expression of β-catenin occurred in 10/12 (83%) diffuse and 8/28 (29%) intestinal tumours (P = 0.0014), and was associated with poor differentiation (P = 0.0015) and short survival (P = 0.032), but not with age, sex, tumour size or nodal status. Nuclear expression of β-catenin was uncommon; cytoplasmic expression was observed in 13/40 cases (33%) but did not correlate with histology, tumour grade or survival. Reduced E-cadherin membrane expression was associated with lymph node metastasis (P = 0.02). Neither E-cadherin or α-catenin expression correlated with survival. Reduced membranous expression of β-catenin predicts poor prognosis in gastric cancer, whilst ectopic intracellular expression is relatively rare. The apparent differences in β-catenin expression from those found in colon cancer merit further study.

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Section: Discussionsupporting

confidence: 62%

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

1999

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“…detergent-soluble fraction (lanes Is and 2s) and insoluble fraction (lane li and 2i), (b) (Kadowaki et al. 1994;Matsui et al, 1994). However, some tumours.…”

Section: Discussionmentioning

confidence: 99%

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line

Shiozaki

Kadowaki²,

Doki³

et al. 1995

Br J Cancer

124

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SummanrEpidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study. we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R. which expresses E-cadherin and EGF receptor. In the presence of EGF. TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate. a tyrosine phosphatase inhibitor, further potentiated the EGF response. whereas herbimycin A. a tvrosine kinase inhibitor, interfered with it. Moreover. EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both a-and P-catenin.cadherin-binding proteins, were also expressed at the same level throughout these morphological changes.Finally. we examined tyrosine phosphorylation of E-cadherin and a-and P-catenin. and observed tyrosine phosphorylation of -catenin induced by EGF. These results suggest that EGF counteracts E-cadherinmediated junctional assembly through phosphorylation of P-catenin and modulates tumour cell behaviour to a more aggressive phenotype.

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“…Immunohistochemical analysis of E-cadherin in gastric cancer specimens has been examined: several studies reported a correlation between E-cadherin loss and the diuse phenotype (Mayer et al, 1993;Matsui et al, 1994;Shino et al, 1995), others found loss of Ecadherin immunoreactivity in only a minority of diuse-type gastric carcinomas (Shimoyama and Hirohashi, 1991;Ochiai et al, 1994). We have analysed the integrity of the E-cadherin mRNA in gastric carcinomas and we detected somatic mutations in 50% of diuse-type gastric carcinomas (Becker et al, 1993(Becker et al, , 1994.…”

Section: Introductionmentioning

confidence: 91%

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

Handschuh¹,

Candidus

Luber³

et al. 1999

Oncogene

188

137

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A major function of the cell-to-cell adhesion molecule Ecadherin is the maintenance of cell adhesion and tissue integrity. E-cadherin de®ciency in tumours leads to changes in cell morphology and motility, so that Ecadherin is considered to be a suppressor of invasion. In this study we investigated the functional consequences of three tumour-associated gene mutations that aect the extracellular portion of E-cadherin: in-frame deletions of exons 8 or 9 and a point mutation in exon 8, as they were found in human gastric carcinomas. Human MDA-MB-435S breast carcinoma cells and mouse L ®broblasts were stably transfected with the wild-type and mutant cDNAs, and the resulting changes in localization of E-cadherin, cell morphology, strength of calcium-dependent aggregation as well as cell motility and actin cytoskeleton organization were studied. We found that cells transfected with wild-type E-cadherin showed an epitheloid morphology, while all cell lines expressing mutant E-cadherin exhibited more irregular cell shapes. Cells expressing Ecadherin mutated in exon 8 showed the most scattered appearance, whereas cells with deletion of exon 9 had an intermediate state. Mutant E-cadherins were localized to the lateral regions of cell-to-cell contact sites. Additionally, both exon 8-mutated E-cadherins showed apical and perinuclear localization, and actin ®laments were drastically reduced. MDA-MB-435S cells with initial calciumdependent cell aggregation exhibited decreased aggregation and, remarkably, increased cell motility, when mutant E-cadherin was expressed. Therefore, we conclude that these E-cadherin mutations may not simply aect cell adhesion but may act in a trans-dominant-active manner, i.e. lead to increased cell motility. Our study suggests that E-cadherin mutations aecting exons 8 or 9 are the cause of multiple morphological and functional disorders and could induce the scattered morphology and the invasive behaviour of diuse type-gastric carcinomas.

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Immunohistochemical evaluation of alpha-catenin expression in human gastric cancer

Cited by 99 publications

References 32 publications

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

Reduction in membranous expression of β-catenin and increased cytoplasmic E-cadherin expression predict poor survival in gastric cancer

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line

Tumour-associated E-cadherin mutations alter cellular morphology, decrease cellular adhesion and increase cellular motility

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