ID4基因高甲基化与乳腺癌相关性研究  

Frequent hypermethylation of ID4 gene promoter in breast cancer

作　　者：张琰[1] 严枫[2] 冯继锋[1] 张晓梅[3] 夏雷[4] 吴剑秋[1] 陈青伟[1] 

机构地区：[1]江苏省肿瘤医院内科,南京210009 [2]江苏省肿瘤医院检验科,南京210009 [3]江苏省肿瘤医院科研科,南京210009 [4]江苏省肿瘤医院病理科,南京210009

出　　处：《临床检验杂志》2014年第8期580-583,共4页Chinese Journal of Clinical Laboratory Science

基　　金：江苏省卫生厅医学领军人才暨创新团队项目(LJ201131);江苏省科技厅临床医学专项(BL2013036)

摘　　要：目的观察乳腺癌中DNA结合抑制因子4(ID4)基因启动子区甲基化状态及其与临床病理特征间的关系,探讨ID4基因在乳腺癌发病过程中的作用机制。方法采用焦磷酸测序法定量检测乳腺癌及正常组织标本中ID4基因启动子区甲基化水平,并分析其在不同临床病理特征间的差异;用RT-PCR检测MM-453细胞去甲基化处理前后ID4启动子区甲基化水平及mRNA表达情况。结果乳腺癌组织中ID4启动子区甲基化水平显著高于正常乳腺组织[(31.16±1.50)%vs(19.89±0.22)%,P<0.01];ER+乳腺癌组织中ID4甲基化水平显著高于ER-乳腺癌组织[(36.57±1.97)%vs(27.91±1.83)%,P<0.01];去甲基化处理后MM-453细胞ID4甲基化水平明显下降,mRNA表达显著上升,两者呈负相关(r=-0.973,P<0.01)。结论 ID4基因可能通过启动子区高甲基化等多种途径在乳腺癌发生、发展过程中起着重要作用,其启动子区高甲基化在ER+的乳腺癌中具有重要意义。Objective To explore the possible mechanism of inhibitor of DNA binding 4 （ID4） gene in breast tumorigenesis by observ- ing the correlations of methylation status of//）4 gene promoter in breast cancer cells with different clinical pathological characteristics. Methods The methylation levels of//）4 promoter region in breast tumor tissue （n = 40） and normal tissue specimens （n = 20） were determined by pyrosequencing and the correlations between the methylation level of ID4 gene and clinical pathological characteristics were analyzed. The methylation levels of ID4 promoter region in MM-453 cell line before and after demethylation treatment were deter- mined by pyrosequencing and the mRNA expression of ID4 was determined by RT-PCR. Results The methylation level of ID4 promoter region in breast tumor tissue was significantly higher than that in normal breast tissue [ （31.16 ±1.50） % vs （ 19.89 ± 0.22） %, P 〈0.01 ]. The methylation level of ID4 gene in ER-positive breast cancer tissue showed significantly higher than that in ER-negative group[ （36.57 ± 1.97） % vs （27.91 ± 1.83） % ,P 〈0.01 ]. The re-expression of 1/）4 gene mRNA was significantly increased and negatively correlated with the methylation of 11）4 in MM-453 cell line （ r = - 0.973, P 〈 0.01 ）. Conclusion ID4 gene may play an important role in breast tumorigenesis and development by a variety of way including hypermethylation of gene promoter, especially in ER-positive breast cancer.

关 键 词：DNA结合抑制因子4基因 乳腺癌 甲基化 焦磷酸测序 

分 类 号：R737[医药卫生—肿瘤]