Identification of Transmembrane Protein in Prostate Cancer by the Escherichia coli Ampicillin Secretion Trap: Expression of CDON Is Involved in Tumor Cell Growth and Invasion
Identification of Transmembrane Protein in Prostate Cancer by the Escherichia coli Ampicillin Secretion Trap: Expression of CDON Is Involved in Tumor Cell Growth and Invasion
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DOI：
10.1159/000329588
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发表时间：
2011-01-01
期刊：
影响因子：
5
通讯作者：
Yasui, Wataru
中科院分区：
文献类型：
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作者：
Hayashi, Tetsutaro;Oue, Naohide;Yasui, Wataru
目的：前列腺癌（Prostate cancer，PCa）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，特别是与位于细胞膜上的蛋白质相关的基因，将成为有用的诊断分子标记物，也可能是良好的治疗靶点。本研究的目的是鉴定编码PCa中存在的跨膜蛋白的基因。方法和结果：我们从2个前列腺癌细胞系和正常前列腺组织中构建了大肠杆菌氨苄青霉素分泌陷阱（CAST）文库。通过对来自CAST文库的3，264个菌落进行测序，我们鉴定了18个编码PCa中存在的跨膜蛋白的候选基因。RT-PCR结果显示STEAP 1、ADAM 9和CDON在PCa中的表达明显高于15种正常组织。在候选者中，CDON编码CDO蛋白，其是免疫球蛋白超家族的孤儿细胞表面受体。另外的定量RT-PCR显示83%的PCa组织显示CDON过表达。在DU 145细胞中敲低CDON可诱导5-氟尿嘧啶诱导的凋亡并抑制侵袭能力。结论：这些结果表明，CDON具有很高的潜力作为治疗PCa的靶点。版权所有（C）2011 S. Karger AG，巴塞尔
Aims: Prostate cancer (PCa) is one of the most common malignancies worldwide. Genes expressed only in cancer tissue, and especially related to proteins located on the cell membrane, will be useful molecular markers for diagnosis and may also be good therapeutic targets. The aim of this study was to identify genes that encode transmembrane proteins present in PCa. Methods and Results: We generated Escherichia coli ampicillin secretion trap (CAST) libraries from 2 PCa cell lines and normal prostate tissues. By sequencing 3,264 colonies from CAST libraries, we identified 18 candidate genes that encode transmembrane proteins present in PCa. Quantitative RT-PCR analysis of these candidates revealed that STEAP1, ADAM9 and CDON were expressed much more highly in PCa than in 15 kinds of normal tissues. Among the candidates, CDON encodes the CDO protein, which is an orphan cell surface receptor of the immunoglobulin superfamily. Additional quantitative RT-PCR revealed that 83% of PCa tissues showed CDON overexpression. Knockdown of CDON in DU145 cells induced 5-fluorouracil-induced apoptosis and inhibited invasion ability. Conclusion: These results suggest that CDON has a high potential as a therapeutic target for PCa. Copyright (C) 2011 S. Karger AG, Basel