IGHMBP2过表达促进食管鳞癌细胞的侵袭和迁移

摘要

IGHMBP2(Immunoglobulin mu binding protein 2)基因编码一种解旋酶，参与DNA的复制和修复，并且作为转录调节因子在基因转录中发挥重要作用。IGHMBP2基因定位于11q13.2，该染色体区段在食管鳞癌中扩增频率较高。为了探讨IGHMBP2基因在食管鳞癌中的扩增情况及其在食管鳞癌中的作用，文章对本实验室前期报道的59例食管鳞癌原发肿瘤array-CGH数据进行分析，结果显示IGHMBP2基因扩增频率为28.9%(17/59)。进一步利用荧光原位杂交(FISH)和Western blot技术，发现食管鳞癌细胞系KYSE30、KYSE180、KYSE510和KYSE150中存在IGHMBP2基因扩增/增益以及蛋白高表达。敲降IGHMBP2后，KYSE30和KYSE150细胞的侵袭迁移能力明显降低(P<0.001)，侵袭迁移相关蛋白E-cadherin的表达水平升高；敲降后转染IGHMBP2质粒，回复其蛋白表达后，细胞的侵袭迁移能力又得以恢复(P<0.01)。上述结果表明，IGHMBP2过表达可能通过降低E-cadherin的表达从而增强食管鳞癌细胞的侵袭迁移能力。%Immunoglobulin mu binding protein 2 (IGHMBP2) is located in 11q13.2, which is frequently amplified in esophageal squamous cell carcinoma (ESCC). IGHMBP2 encodes a helicase involved in DNA replication and re-pair. IGHMBP2 protein also regulates gene transcription. The present study aims to explore the amplification of IGHMBP2 and its potential role in ESCC. A further analysis of our previously reported array-CGH data showed that IGHMBP2 was amplified in 28.9% of primary ESCC tumors. Fluorescence in situ hybridization (FISH) and West-ern blot showed that IGHMBP2 was amplified and overexpressed in KYSE30, KYSE180, KYSE510 and KYSE150 esophageal cancer cell lines. Transwell assays demonstrated that knockdown of IGHMBP2 in KYSE30 and KYSE150 inhibited cell invasion and migration, and increased the expression levels of E-cadherin. When rescue plasmids ex-pressing IGHMBP2 were introduced, the abilities of cell invasion and migration were restored. These data suggest that IGHMBP2 overexpression may promote invasion and migration of ESCC cells through down-regulation of E-cadherin.