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. 2000 May;46(5):639–644. doi: 10.1136/gut.46.5.639

α-Catenin expression is decreased in human gastric cancers and in the gastric mucosa of first degree relatives

J Yu 1, M Ebert 1, S Miehlke 1, H Rost 1, U Lendeckel 1, A Leodolter 1, M Stolte 1, E Bayerdorffer 1, P Malfertheiner 1
PMCID: PMC1727909  PMID: 10764706

Abstract

BACKGROUND AND AIMS—The role of altered cell adhesion is critical for the development of epithelial cancers. E-cadherin plays an important role in the maintenance of cell-cell adhesion and its function is thought to be regulated by its associated cytoplasmic proteins, such as α-catenin and β-catenin. To determine the role of α-catenin expression in gastric carcinogenesis, we studied its expression in human gastric cancer and in the gastric mucosa of first degree relatives with no clinical disease.
METHODS—α-Catenin expression was assessed by immunohistochemical analysis and reverse transcriptase-polymerase chain reaction (RT-PCR) using gastric tissue specimens from patients with gastric cancer and from the gastric mucosa of first degree relatives of gastric cancer patients and healthy controls.
RESULTS—mRNA levels of α-catenin were reduced or absent in 13 of 19 gastric cancer tissues, which differed significantly from levels found in the tumour free gastric mucosa of cancer patients (p<0.05). Of the cancer samples with altered α-catenin mRNA levels, α-catenin expression was negative in seven and decreased in six cases. Interestingly, decreased α-catenin mRNA expression also occurred in the mucosa of the corpus (11/18) and antrum (4/18) of first degree relatives. In the corpus biopsies α-catenin expression was more often decreased or lost compared with the antrum biopsies in first degree relatives and healthy controls (p<0.05). Immunohistochemical analysis revealed membranous expression of α-catenin in gastric cancer cells and the non-malignant gastric epithelium. However, some cancers also exhibited loss of membranous staining. Generally, loss or downregulation of α-catenin mRNA in the gastric mucosa was associated with Helicobacter pylori infection (p<0.05).
CONCLUSION—Our findings suggest that loss or downregulation of α-catenin expression may be an early event in gastric carcinogenesis and may be associated with H pylori infection.


Keywords: risk; stomach; gene; cadherins; gastric cancer; α-catenin

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Figure 1  .

Figure 1  

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RT-PCR analysis of α-catenin mRNA in gastric tissues. RT-PCR analysis was performed using specific primers for human α-catenin as described in materials and methods. Amplification of β-actin mRNA was performed to ensure equal loading. Lanes 1-2: tumour free and tumour from patient No 1; lanes 3-4: corpus and antrum from relative No 6; lanes 6-7: tumour free and tumour from patient No 2; lanes 8-9: corpus and antrum from relative No 2; lanes 5 and 10: gastric mucosa from healthy subjects; lane 11: negative control; and lane 12: DNA ladder.

Figure 2  .

Figure 2  

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Semiquantitative RT-PCR analysis of α-catenin expression. NT, non-tumour; T, tumour; C, corpus from first degree relatives; A, antrum from first degree relatives; N, healthy subjects. *p<0.05.

Figure 3  .

Figure 3  

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Immunohistochemical analysis of α-catenin expression. In the normal gastric epithelium, α-catenin immunoreactivity was located at the cell membrane (A, arrowheads) and in the cytoplasm. Gastric cancer cells exhibited various levels of cytoplasmic and/or membranous immunoreactivity in diffuse-type (B) or intestinal-type (C) gastric carcinoma. In some cases α-catenin immunoreactivity was decreased in the gastric cancer cells (C).

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