Dystroglycan expression is frequently reduced in human breast and colon cancers and is associated with tumor progression
Dystroglycan expression is frequently reduced in human breast and colon cancers and is associated with tumor progression
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DOI：
10.1016/s0002-9440(10)63881-3
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发表时间：
2003-03-01
影响因子：
6
通讯作者：
Cittadini, A
中科院分区：
文献类型：
--
作者：
Sgambato, A;Migaldi, M;Cittadini, A
Dystroglycan（DG）是细胞外基质与细胞质间相互作用的重要粘附分子。它由两个亚基α-DG（细胞外）和β-DG（跨膜）形成，分别与基质中的层粘连蛋白和细胞骨架中的肌营养不良蛋白结合。在这项研究中，我们通过Western印迹分析评估了DG在一系列不同组织发生起源的人癌细胞系和一系列人原发性结肠癌和乳腺癌中的表达。DG的表达减少，观察到在大多数的细胞系和两种类型的肿瘤，并与较高的肿瘤分级和阶段。mRNA水平的分析表明，DG蛋白的表达可能是在转录后水平调节。通过免疫染色评估α-DG表达;在一系列原发性乳腺癌的存档病例中证实，α-DG表达在相当大一部分肿瘤中丢失（66%）。DG染色的缺失与较高的肿瘤分期（P = 0.022）、p53阳性（P = 0.033）和高增殖指数（P = 0.045）相关。在单因素分析中也观察到α-DG丢失与总生存率之间的显著相关性（P = 0.013，通过对数秩检验）。这些数据表明，DG的表达经常在人类恶性肿瘤中丢失，并表明这种糖蛋白可能在人类肿瘤的发展和进展中发挥重要作用。
Dystroglycan (DG) is an adhesion molecule responsible for crucial interactions between extracellular matrix and cytoplasmic compartment. It is formed by two subunits, alpha-DG (extracellular) and beta-DG (transmembrane), that bind to laminin in the matrix and dystrophin in the cytoskeleton, respectively. in this study we evaluated by Western blot analysis the expression of DG in a series of human cancer cell lines of various histogenetic origin and in a series of human primary colon and breast cancers. Decreased expression of DG was observed in most of the cell lines and in both types of tumors and correlated with higher tumor grade and stage. Analysis of the mRNA levels suggested that expression of DG protein is likely regulated at a posttranscriptional level. Evaluation of alpha-DG expression by immunostaining; in a series of archival cases of primary breast carcinomas confirmed that alpha-DG expression is lost in a significant fraction of tumors (66%). Loss of DG staining correlated with higher tumor stage (P = 0.022), positivity for p53 (P = 0.033), and high proliferation index (P = 0.045). A significant correlation Was also observed between loss of alpha-DG and overall survival (P = 0.013 by log-rank test) in an univariate analysis. These data indicate that DG expression is frequently lost in human malignancies and suggest that this glycoprotein might play an important role in human tumor development and progression.