利用大肠杆菌氨苄青霉素分泌陷阱鉴定前列腺癌细胞中的跨膜蛋白：CDON 的表达参与肿瘤细胞的生长和侵袭。

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.

机构信息

Department of Molecular Pathology, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.

出版信息

Pathobiology. 2011;78(5):277-84. doi: 10.1159/000329588. Epub 2011 Aug 17.

DOI:10.1159/000329588

PMID:21849809

Abstract

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.

摘要

目的

前列腺癌（PCa）是全球最常见的恶性肿瘤之一。仅在癌组织中表达的基因，特别是与细胞膜上的蛋白质相关的基因，将是诊断有用的分子标志物，也可能是良好的治疗靶点。本研究旨在鉴定编码 PCa 中存在的跨膜蛋白的基因。

方法和结果

我们从 2 种 PCa 细胞系和正常前列腺组织中生成了大肠杆菌氨苄青霉素分泌陷阱（CAST）文库。通过对 CAST 文库中 3264 个菌落进行测序，我们鉴定出 18 个候选基因，这些基因编码 PCa 中存在的跨膜蛋白。对这些候选基因进行定量 RT-PCR 分析表明，STEAP1、ADAM9 和 CDON 在 PCa 中的表达水平明显高于 15 种正常组织。在候选基因中，CDON 编码 CDO 蛋白，CDO 蛋白是免疫球蛋白超家族的孤儿细胞表面受体。进一步的定量 RT-PCR 显示，83%的 PCa 组织存在 CDON 过表达。在 DU145 细胞中敲低 CDON 可诱导 5-氟尿嘧啶诱导的细胞凋亡，并抑制侵袭能力。