目的：应用高通量基因芯片技术筛查乳腺癌细胞中黑色素瘤相关抗原（melanoma antigen，MAGE）-A11 的相关基因，并从数量和功能两方面加以验证。方法：采用基因芯片技术筛选乳腺癌MCF-7、MDA-MB-231 和BT-549 中MAGE-A11 下游靶基因的mRNA的差异表达，对有代表性的基因进行了聚类分析，并利用qRT-PCR进行验证。以CCK-8 法、细胞划痕实验和Transwell实验检测MAGE-A11 对乳腺癌细胞中增殖、迁移和侵袭功能的影响。结果：3 种乳腺癌细胞过表达MAGE-A11 导致1 608个下游基因差异表达，主要涉及蛋白泛素化、细胞增殖和凋亡、肿瘤侵袭和转移。基因芯片中典型高表达的ZNF-451、CENPTJ、CDK13、API5 和LMO7 在qRT-PCR 在验证结果中也显著高于对照组（P<0.01），低表达的SHPRH、PML、MARK2、LIMA1 和ANGPTL4也显著低于对照组（P<0.01）。转染MAGE-A11 组的乳腺癌细胞MCF-7、MDA-MB-231 和BT-549 72 h 的增殖能力较对照组明显增强（均P<0.01），培养48 h 后与对照组相比，转染MAGE-A11 的3 种细胞划痕出现明显愈合（P<0.05 或P<0.01），穿膜数较对照组明显增多（均P<0.01）。结论：在MCF-7、MDA-MB-231 和BT-549 三种乳腺癌细胞中筛查到涉及蛋白泛素化、细胞增殖和凋亡、肿瘤侵袭和迁移等生物功能众多的表达差异基因，对其中10 种典型差异基因从数量和功能两方面进行验证，并得到初步确认。

Objective: To screen related genes of melanoma-associated antigen-A11 (MAGE-A11) in breast cancer cells based on highthroughput DNA microarray technology, and to validate from the aspects of quantity and function. Methods: DNA microarray was used to screen the differently-expresseddown-stream mRNAs of MAGE-A11 in breast cancercelllines (MCF-7, MDA-MB-231 and BT-549).Cluster analysis was applied on representative genes and quantitative RT-PCR was used to validate. CCK-8, scratch wound healing assay and Transwell assaywere used to detect the effect of MAGE-A11 on the proliferation,migration and invasion of breast cancer cells.Results: Over-expression of MAGE-A11 caused the differential expression of 1608 down-stream genes in 3 breast cancer cell lines,which was associated with various cell functions such as protein ubiquitination,cell proliferation and apoptosis, tumor invasion and metastasis.qRT-PCR validated that the expression of ZNF-451, CENPTJ, CDK13, API5 and LMO7, which were highly expressed in microarray,were also significantly higher than those in control group (P<0.01);in addition, SHPRH, PML, MARK2, LIMA1 and ANGPTL4,which were low-expressed in microarray, were also significantly lower than those in control group (P<0.01). MAGE-A11transfection directly increased the proliferation of breast cancer MCF-7, MDA-MB-231 and BT-549 cells at 72 h (all P<0.01); compared with control group after transfectionexhibited obvious wound healing at 48 h (P<0.05 or P<0.01) and significantly increased trans-membrane cell numbers (all P<0.01). Conclusion: Many differentially expressed genes related to ubiquitination, cell proliferation and apoptosis, tumor invasion and migration were screened in MCF-7, MDA-MB-231 and BT-549 breast cancer cells. Among them, 10 typical differentially expressed genes were identified in terms of quantity and function.

河北省科技计划资助项目（No.152777184）；河北省杰出青年基金资助项目（No.H2016206410）；河北省财政厅资助项目（No.[2016]361006）