乳腺癌中NDRG1基因甲基化状态的研究.docVIP

乳腺癌中NDRG1基因甲基化状态的研究 　　 [摘要] 目的 研究NDRG1基因启动子区甲基化状态，探讨NDRG-1基因甲基化在乳腺癌发生中的作用。方法 采用双色荧光杂交微阵列基因芯片技术对33对乳腺癌标本和癌旁组织标本NDRG-1基因启动子区甲基化状态进行研究。结果 肿瘤标本和癌旁组织标本中NDRG-1基因启动子区CpG位点均有不同程度的甲基化，肿瘤组织中NDRG-1基因启动子区CpG位点甲基化率明显高于相应的癌旁组织（t=14.12，P0.05）。结论 NDRG-1基因启动子区过甲基化可能在乳腺癌的发生过程中起重要作用。? 　　［关键词］ 乳腺癌；甲基化;NDRG-1基因? 　　［中图分类号］ R735 [文献标识码] Ａ [文章编号] 1671-7562（2008）02-0079-05?? 　　 　　The methylation status of CpG island in the promoter? 　　 region of NDRG-1 gene in breast cancer?? 　　WANG Li-wei?1，ZHOU Dong-rui?2，FANG Ru-jing?2，ZAHNG Ren-min?2，LU Zu-hong?2，HE Jie?1 　　（1.Department of Pathology,Zhongda Hospital,School of Clinical Medicine,Southeast University,Nanjing 210009,China;?2.State Key Laboratory of Bioelectronics,Southeast University,Nanjing 210096,China)?? 　　Abstract:Objective To explore the correlations of methylation status in the promoter region of NDRG1 geneto carcinogenesis of breast cancer.Methods Microarray-based methylation analysis was used to detect the methylation status in the promoter region of NDRG1 gene in 33 pairs of breast cancer and corresponding normal tissues.Results The methylation level of CpG island in the promoter region of NDRG1 gene in breast cancer was higher than that in tissues adjacent（t=14.12，P0.05）.Conclusion Hypermethylation of CpG island in the promoter region of NDRG-1 gene possibly plays important role in carcinogenesis of breast cancer.? 　　Key words:breast cancer;methylation;NDRG-1 gene? 　　（Modern Medical Journal,2008,36:79-83）?? 　　 　　 NDRG-1基因（Ｎ-myc downstream regulated gene 1）又称Drg-1[1](differentiation related gene 1，分化相关基因)、RTP[2]（reducing agents and tunicamycin responsive protein，还原剂和衣霉素敏感蛋白）、Cap43[3](calcium activated protein 43，钙激活蛋白43)、Rit42[2]（reduced in tumor 42）和PROXY-1[4](protein regulated by OXYen-1，氧调节蛋白)。NDRG-1基因是近年来发现的与细胞分化相关的新基因，作为候选的抑癌基因，具有调控肿瘤细胞分化、抑制肿瘤细胞转移和生长的功能，并且能够在诱导分化剂作用下表达增加，NDRG-1基因与多种肿瘤的发生发展相关，如直结肠癌、乳腺癌、肝细胞癌等[5]。有研究表明，NDRG-1基因的表达与乳腺癌的转移呈负相关，它能抑制肿瘤细胞增殖、降低其侵袭能力，可作为一个候选的肿瘤抑制基因，并有望成为乳腺癌基因治疗新的候选基因[6]。目前更倾向于NDRG-1基因在乳腺癌