Jung Eun Ji, Kim Min A, Lee Hye Seung, Yang Han Kwang, Lee You Mie, Lee Byung Lan, Kim Woo Ho
Department of Pathology, Seoul National University College of Medicine, Seoul 110-799, Korea.
Anticancer Res. 2005 May-Jun;25(3B):2105-11.
Since the members of the MAGE (melanoma antigen) gene family have been reported to be expressed in tumor cells but not in normal tissues, they have been considered as targets for tumor-specific immunotherapy.
The expression pattern of MAGE-A genes and their expression mechanisms were investigated in 10 gastric cancer cell lines and 1,097 gastric carcinoma specimens by RT-PCR, IHC, Western blot and MSP.
MAGE-A1, -A2 and -A3 gene transcripts were detected in 1, 3 and 4 of 10 gastric cancer cell lines, respectively. In those cases in which the mRNA expression of MAGE-A2 or -A3 was detected, the promoters of the corresponding genes were hypomethylated. MAGE-A protein expression was detected in 30% (3/10) of the cell lines and 15.8% (173 out of 1,097) of the carcinoma specimens. Promoter hypomethylation of the MAGE-A2 or -A3 genes correlated with their expression in primary gastric cancer tissue and gastric cancer cell lines. MAGE-A protein expression was associated with tumor invasiveness (p=0.002), lymph node metastasis (p<0.001), advanced pathologic stage (p<0.001) and a worse prognosis (p<0.005).
MAGE-A protein expression occurred due to promoter hypomethylation in a minor subset of gastric cancers, and MAGE-A expression increased during the progression of the gastric cancer.
由于黑色素瘤抗原（MAGE）基因家族成员据报道在肿瘤细胞中表达，而在正常组织中不表达，因此它们被视为肿瘤特异性免疫治疗的靶点。
采用逆转录聚合酶链反应（RT-PCR）、免疫组织化学（IHC）、蛋白质免疫印迹法（Western blot）和甲基化特异性PCR（MSP），对10株胃癌细胞系和1097例胃癌标本中MAGE-A基因的表达模式及其表达机制进行了研究。
在10株胃癌细胞系中，分别有1株、3株和4株检测到MAGE-A1、-A2和-A3基因转录本。在检测到MAGE-A2或-A3 mRNA表达的病例中，相应基因的启动子发生低甲基化。在30%（3/10）的细胞系和15.8%（1097例中的173例）的癌标本中检测到MAGE-A蛋白表达。MAGE-A2或-A3基因的启动子低甲基化与其在原发性胃癌组织和胃癌细胞系中的表达相关。MAGE-A蛋白表达与肿瘤侵袭性（p=0.002）、淋巴结转移（p<0.001）、病理分期较晚（p<0.001）及预后较差（p<0.005）相关。
在一小部分胃癌中，MAGE-A蛋白表达是由于启动子低甲基化所致，且MAGE-A表达在胃癌进展过程中增加。
