Search for transmembrane protein in gastric cancer by the Escherichia coli ampicillin secretion trap: expression of DSC2 in gastric cancer with intestinal phenotype
Search for transmembrane protein in gastric cancer by the Escherichia coli ampicillin secretion trap: expression of DSC2 in gastric cancer with intestinal phenotype
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DOI：
10.1002/path.2717
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发表时间：
2010-07-01
影响因子：
7.3
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
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作者：
Anami, Katsuhiro;Oue, Naohide;Yasui, Wataru
胃癌是世界范围内最常见的恶性肿瘤之一。仅在癌组织中表达的基因，特别是在细胞膜上表达的基因，将是用于诊断的有用的分子标记物，也可能是良好的治疗靶点。为了鉴定编码GC中存在的跨膜蛋白的基因，我们从两个GC细胞系和正常胃中产生了大肠杆菌氨苄青霉素分泌陷阱（CAST）文库。通过对CAST文库中的4320个克隆进行测序，我们确定了30个编码GC中存在的跨膜蛋白的候选基因。定量逆转录-聚合酶链反应分析显示，ZDHHC 14、BST 2、DRAM 2和DSC 2在胃癌中的表达明显高于14种正常组织。其中，DSC 2编码桥粒胶蛋白2，其是三种已知的桥粒胶蛋白之一。免疫组化结果显示，80例胃癌中有22例（28%）表达桥粒胶蛋白2，且桥粒胶蛋白2在肠粘蛋白表型胃癌中表达频繁。此外，桥粒胶原2表达与CDX 2表达相关。这些结果表明，由CDX 2诱导的桥粒胶蛋白2的表达可能是具有肠粘蛋白表型的GC的关键调节因子。我们的研究结果提供了一个基因列表，这些基因具有很高的潜力作为GC的诊断和治疗靶点。版权所有（C）2010大不列颠和爱尔兰病理学会。由John Wiley & Sons有限公司出版
Gastric cancer (GC) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue, and especially on the cell membrane, will be useful molecular markers for diagnosis and may also be good therapeutic targets. To identify genes that encode transmembrane proteins present in GC, we generated Escherichia coli ampicillin secretion trap (CAST) libraries from two GC cell lines and normal stomach. By sequencing 4320 colonies from CAST libraries, we identified 30 candidate genes that encode transmembrane proteins present in GC. Quantitative reverse transcription-polymerase chain reaction analysis of these candidates revealed that ZDHHC14, BST2, DRAM2, and DSC2 were expressed much more highly in GC than in 14 kinds of normal tissues. Among these, DSC2 encodes desmocollin 2, which is one of three known desmocollins. Immunohistochemical analysis demonstrated that 22 (28%) of 80 GC cases were positive for desmocollin 2, and desmocollin 2 expression was observed frequently in GC with the intestinal mucin phenotype. Furthermore, desmocollin 2 expression was correlated with CDX2 expression. These results suggest that expression of desmocollin 2, induced by CDX2, may be a key regulator for GC with the intestinal mucin phenotype. Our results provide a list of genes that have high potential as a diagnostic and therapeutic target for GC. Copyright (C) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.