目的：探讨黑素瘤抗原MAGE-A9和MAGE-A11 在乳腺正常组织、乳腺良性病变、乳腺癌组织中的表达以及甲基化酶抑制剂5-氮杂-2′-脱氧胞苷 (5-Aza-2’-deoxycytidine, 5-Aza-CdR)和组蛋白去乙酰化酶抑制剂曲古抑菌素A（TSA）对MAGE-A9和MAGE-A11 基因表达的影响。方法：应用RT-PCR和免疫组化方法检测60例乳腺正常组织、60例乳腺良性病变及60例乳腺癌组织（标本均取自河北医科大学第四医院乳腺中心2007年11月至2008年5月乳腺手术治疗患者）中MAGE-A9和MAGE-A11 mRNA及其蛋白的表达，分析其与乳腺癌患者临床病理学特征的关系。RT-PCR检测乳腺癌细胞MCF-7、MDA-MB-231经5-Aza-CdR 和 TSA 单独或联合作用后MAGE-A9和MAGE-A11 mRNA 表达量的变化。结果：乳腺癌组织中MAGE-A9 mRNA和蛋白阳性表达率分别为45%（27/60）和43.3%（26/60），MAGE-A11 mRNA和蛋白阳性表达率分别为66.7%（40/60）和63.3%（38/60），而乳腺正常组织及良性病变组织中均未发现MAGE-A9、MAGE-A11 mRNA及其蛋白的表达。 MAGE-A9、MAGE-A11 mRNA和蛋白的表达与乳腺癌患者的年龄、病理类型、临床分期、肿瘤大小、淋巴转移、瘤栓及孕激素受体的表达均无明显关系（P>0.05），但与人表皮生长因子受体2（HER-2）和雌激素受体（ER）的表达有关（P<0.05）。未经药物处理的MCF-7、MDA-MB-231细胞未见MAGE-A9和MAGE-A11 mRNA表达；单用5-Aza-CdR处理后可见MAGE-A9和MAGE-A11 基因重新表达，联合应用5-Aza-CdR和TSA处理可使MAGE-A9、MAGE-A11基因的表达量进一步增加（P<0.05）；而TSA单独处理对基因表达没有影响（P>0.05）。结论：乳腺癌组织中MAGE-A9和MAGE-A11 的表达与ER 和HER-2的表达有关，5-Aza-CdR单用或联合应用TSA可诱导和增强MAGE-A9和MAGE-A11 mRNA的重新表达，说明DNA的去甲基化和组蛋白乙酰化可能是调控人类肿瘤细胞MAGE表达的重要机制。

Objective: The purpose of our study was to analyze the expression of melanoma antigen genes MAGE-A9 and MAGE-A11 in benign and malignant breast cancer specimens and in breast cancer cell lines following drug treatment. Methods: Tissue specimens were obtained from tumor-free breast (n=60), benign breast cancer (n=60) and malignant breast cancer (n=60), respectively. The mRNA abundance and protein content of MAGE-A9 and MAGE-A11 in these specimens were determined by RT-PCR and immunohistochemistry respectively and were analyzed for their associations with the major demographic, physiologic and pathologic variables. To examine the influence of chemotherapeutic drugs on MAGEs in breast cancer, MCF-7 and MDA-MB-231 cells were treated with 5-Aza-2’-deoxycytidine (5-Aza-CdR), a DNA methylase inhibitor, and trichostatin A (TSA), a histone deacetylase inhibitor, either each alone or both together, and mRNA levels of MAGE-A9 and MAGE-A11 were assessed by RT-PCR. Results：MAGE-A9 and MAGE-A11 transcripts were detected in 45% and 66.7% of breast cancer specimens respectively and MAGE-A9 and MAGE-A11 proteins in 433% and 63.3% of cancer specimens, respectively. MAGE-A9 and MAGE-A11 expression was positively correlated with the expression of estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER-2) in cancer specimens (P<0.05). Neither transcripts nor proteins of MAGE-A9 and MAGE-A11 were detected in normal control specimens. While 5-Aza-CdR alone induced the expression of MAGE-A9 and MAGE-A11 in the test cell lines, TSA alone showed no effects. However, TSA was able to enhance 5-Aza-CdR-induced MAGE-A transcription (P<0.01).Conclusion：MAGE-A9 and MAGE-A11 are tumor-specific antigens. Both DNA hypermethylation and histone deacetylation are possible mechanisms underlying MAGE-A9 and MAGE-A11 gene silencing.

河北省自然科学基金资助项目（No.H2012206077）。