Lee Taek Sang, Kim Jae Weon, Kang Gyeong Hoon, Park Noh Hyun, Song Yong Sang, Kang Soon Beom, Lee Hyo Pyo
Department of Obstetrics and Gynecology and Cancer Research Institute, College of Medicine, Seoul National University, 28 Yungun-Dong, Chongno-Ku, Seoul 110-744, South Korea.
Ann N Y Acad Sci. 2006 Dec;1091:218-24. doi: 10.1196/annals.1378.068.
This study was performed to determine whether promotor hypomethylation of CAGE is involved in cervical carcinogenesis. The surgical specimens of 40 cervical squamous cell carcinoma patients treated at Seoul National University Hospital and those of 48 healthy controls were used, with informed consent. We investigated the promotor hypomethylation status of CAGE by methylation-specific polymerase chain reaction (MSP) using primers specific for unmethylated sequences, and found hypomethylation of CAGE promotor at a frequency approaching 90% in cervical squamous cell carcinomas (35/40, 87.5%), but at less than 4% in controls (P < 0.001). This finding provides experimental evidence of the frequent hypomethylation of normally methylated CAGE promotor CpG islands in cervical cancer, and indicates that this hypomethylation is likely to be a valuable surrogate marker for the expression of CAGE. It also provides a clue concerning the molecular mechanisms of carcinogenesis in cervical squamous cell carcinoma.
本研究旨在确定CAGE启动子低甲基化是否参与宫颈癌的发生。使用了首尔国立大学医院治疗的40例宫颈鳞状细胞癌患者的手术标本以及48例健康对照者的标本,并获得了知情同意。我们使用针对未甲基化序列的引物,通过甲基化特异性聚合酶链反应(MSP)研究了CAGE启动子的低甲基化状态,发现在宫颈鳞状细胞癌中CAGE启动子低甲基化的频率接近90%(35/40,87.5%),而在对照中低于4%(P < 0.001)。这一发现为宫颈癌中正常甲基化的CAGE启动子CpG岛频繁发生低甲基化提供了实验证据,并表明这种低甲基化可能是CAGE表达的一个有价值的替代标志物。它还为宫颈鳞状细胞癌的致癌分子机制提供了线索。