Yu J, Ebert M P, Miehlke S, Rost H, Lendeckel U, Leodolter A, Stolte M, Bayerdörffer E, Malfertheiner P
Department of Gastroenterology, Hepatology, and Infectious Diseases, Otto-von-Guericke University, D-39120 Magdeburg, Germany.
Gut. 2000 May;46(5):639-44. doi: 10.1136/gut.46.5.639.
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 alpha-catenin and beta-catenin. To determine the role of alpha-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.
alpha-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.
mRNA levels of alpha-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 alpha-catenin mRNA levels, alpha-catenin expression was negative in seven and decreased in six cases. Interestingly, decreased alpha-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 alpha-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 alpha-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 alpha-catenin mRNA in the gastric mucosa was associated with Helicobacter pylori infection (p<0.05).
Our findings suggest that loss or downregulation of alpha-catenin expression may be an early event in gastric carcinogenesis and may be associated with H pylori infection.
细胞黏附改变在上皮癌发生过程中起关键作用。E-钙黏蛋白在维持细胞间黏附中起重要作用,其功能被认为受相关胞质蛋白如α-连环蛋白和β-连环蛋白调控。为确定α-连环蛋白表达在胃癌发生中的作用,我们研究了其在人类胃癌及无临床疾病的一级亲属胃黏膜中的表达情况。
采用免疫组织化学分析及逆转录聚合酶链反应(RT-PCR),利用胃癌患者的胃组织标本、胃癌患者一级亲属及健康对照者的胃黏膜标本评估α-连环蛋白表达。
19例胃癌组织中有13例α-连环蛋白的mRNA水平降低或缺失,这与癌患者无肿瘤的胃黏膜中发现的水平有显著差异(p<0.05)。在α-连环蛋白mRNA水平改变的癌样本中,α-连环蛋白表达7例为阴性,6例降低。有趣的是,一级亲属胃体(11/18)和胃窦(4/18)的黏膜中也出现α-连环蛋白mRNA表达降低。在一级亲属和健康对照者中,胃体活检标本中α-连环蛋白表达比胃窦活检标本更常降低或缺失(p<0.05)。免疫组织化学分析显示α-连环蛋白在胃癌细胞及非恶性胃上皮中呈膜性表达。然而,一些癌症也表现出膜性染色缺失。一般来说,胃黏膜中α-连环蛋白mRNA的缺失或下调与幽门螺杆菌感染相关(p<0.05)。
我们的研究结果表明,α-连环蛋白表达的缺失或下调可能是胃癌发生的早期事件,且可能与幽门螺杆菌感染有关。