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鳞状细胞癌中肌营养不良聚糖的异常表达、加工与降解

Aberrant expression, processing and degradation of dystroglycan in squamous cell carcinomas.

作者信息

Jing Jie, Lien Chun Fu, Sharma Sanjay, Rice Jill, Brennan Peter A, Górecki Dariusz C

机构信息

School of Pharmacy and Biomedical Sciences, Institute of Biomedical and Biomolecular Sciences, Molecular Medicine Group, University of Portsmouth, St. Michael's Building, White Swan Road, PO1 2DT, UK.

出版信息

Eur J Cancer. 2004 Sep;40(14):2143-51. doi: 10.1016/j.ejca.2004.05.018.

Abstract

The alpha- and beta- dystroglycan (DG) proteins are involved in epithelial cell development, formation of the basement membrane and maintenance of tissue integrity. Recently, specific changes in the expression patterns of DGs have been described in some cancers. We studied the expression and localisation of alpha- and beta-DG using Western blotting, immunohistochemistry and reverse transcriptase-polymerase chain reaction analyses in samples of normal oral mucosa, oral squamous cell carcinoma (SCC) and cancer cell lines. The alpha- and beta-DG were localised in the basal layers of normal oral mucosa.However, beta-DG expression in cancer tissues showed evidence of aberrant expression, processing and degradation. alpha-DG was altered in all oral cancer samples and cell lines, despite the persistent presence of DG mRNA in cancer cells. Using matrix metalloproteinase (MMP) inhibitors, we determined that beta-DG degradation in carcinoma cell lines can be mediated by MMPs but this process is highly variable, even in cells from the same cancer type. Considering the multifaceted role of DG in epithelial development, it appears that the role of DG degradation in cancer growth and spread, although currently poorly understood, may be important.

摘要

α-和β-肌营养不良蛋白聚糖(DG)参与上皮细胞发育、基底膜形成及组织完整性维持。近来,在一些癌症中已描述了DG表达模式的特定变化。我们运用蛋白质免疫印迹法、免疫组织化学及逆转录聚合酶链反应分析,研究了α-和β-DG在正常口腔黏膜、口腔鳞状细胞癌(SCC)样本及癌细胞系中的表达与定位。α-和β-DG定位于正常口腔黏膜的基底层。然而,癌组织中的β-DG表达显示出异常表达、加工及降解的迹象。尽管癌细胞中持续存在DG mRNA,但所有口腔癌样本及细胞系中的α-DG均发生了改变。使用基质金属蛋白酶(MMP)抑制剂,我们确定癌细胞系中β-DG的降解可由MMP介导,但即便在同一癌症类型的细胞中,这一过程也高度可变。鉴于DG在上皮发育中的多方面作用,DG降解在癌症生长和扩散中的作用尽管目前了解甚少,但似乎可能很重要。

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