Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin
Proteomic analysis of primary esophageal squamous cell carcinoma reveals downregulation of a cell adhesion protein, periplakin
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DOI：
10.1002/pmic.200500262
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发表时间：
2006-02-01
期刊：
影响因子：
3.4
通讯作者：
Ochiai, T
中科院分区：
文献类型：
--
作者：
Nishimori, T;Tomonaga, T;Ochiai, T
二维电泳（2-DE）如荧光2-D差异凝胶电泳（2-D DIGE）的最新进展使得检测和定量涉及疾病发病机制的关键变化成为可能。我们以前已经确定了新的蛋白质与改变表达的原发性结直肠癌使用琼脂糖2-DE，具有更高的负载能力比固定PH梯度凝胶。本研究的目的是利用琼脂糖双向凝胶电泳和琼脂糖双向凝胶电泳技术，鉴定原发性食管癌中表达改变的新蛋白。本文收集了12例原发性食管癌患者的手术切除组织。通过琼脂糖2-D DIGE分析癌组织和邻近非癌组织之间表达改变的蛋白质，并通过质谱法鉴定。在74个肿瘤表达改变的蛋白质点中鉴定出33个。其中，一个195 kDa的蛋白，periplakin，在食管癌中显着下调，这是由免疫印迹证实。免疫组化结果显示，periplakin在正常上皮和不典型增生病变中主要定位于细胞-细胞边界，而在早期癌中periplakin从细胞边界消失，转移到胞浆，在晚期癌中几乎不表达。这些结果表明，periplakin可能是一个有用的标志物，用于检测早期食管癌和评估肿瘤进展。
Recent advances in two-dimensional electrophoresis; (2-DE) such as fluorescent 2-D differential gel electrophoresis (2-D DIGE) has made it possible to detect and quantitate the critical changes involved in disease pathogenesis. We have previously identified novel proteins with altered expression in primary colorectal cancer using agarose 2-DE that has a higher loading capacity than immobilized PH gradient gel. The aim of this study is to identify novel proteins with altered expression in primary esophageal cancer using the powerful method of agarose 2-DE and agarose 2-D DIGE. Excised tissues from 12 patients of primary esophageal cancer were obtained. Proteins with altered expression between cancer and adjacent non-cancer tissues were analyzed by agarose 2-D DIGE and identified by mass spectrometry. Thirty-three proteins out of 74 spots with altered expression in tumors were identified. Among them, a 195-kDa protein, periplakin, was significantly downregulated in esophageal cancer, which was confirmed by immunoblotting. Immunohistochemistry showed that periplakin was mainly localized at cell-cell boundaries in normal epithelium and dysplastic lesions, while it disappeared from cell boundaries, shifted to cytoplasm, in early cancers and scarcely expressed in advanced cancers. These results suggest that periplakin could be a useful marker for detection of early esophageal cancer and evaluation of tumor progression.