天津医药

天津医药 ›› 2015, Vol. 43 ›› Issue (5): 500-504.doi: 10.11958/j.issn.0253-9896.2015.05.014

• 临床研究 • 上一篇    下一篇

散发性乳腺癌中DNMT3a、DNMT3b表达与 ERα基因启动子甲基化状态及蛋白表达的关系

王勇 1， 王晓东 2， 陈文捷 2， 于兆进 2， 吴慧哲 2， 赵琳 2， 魏敏杰 2△#br#   

  1. 1中国医科大学药学院办公室 （邮编110013）； 2中国医科大学药学院药理学教研室
  • 收稿日期:2014-10-21 修回日期:2014-12-19 出版日期:2015-05-15 发布日期:2015-05-25
  • 通讯作者: 王晓东 E-mail:mjwei@hotmail.com E-mail:15063831558@163.com
  • 作者简介:王勇 （1980）， 男， 硕士， 主要从事分子肿瘤药理学研究
  • 基金资助:
    辽宁省高校创新团队支持计划资助项目 （LT2014016）

The association of DNMT3a, DNMT3b expression with the state of promoter methylation of ERα gene and ERα expression in sporadic breast cancer

WANG Yong1, WANG Xiaodong2, CHEN Wenjie2, YU Zhaojin2, WU Huizhe2, ZHAO Lin2， WEI Minjie2△#br# #br#   

  1. 1 Department of Pharmacology, China Medical University, Shenyang 110013,China; 2 Department of Pharmacology, The Pharmaceutical School of China Medical University
  • Received:2014-10-21 Revised:2014-12-19 Published:2015-05-15 Online:2015-05-25
  • Contact: Xiao-Dong WANG E-mail:mjwei@hotmail.com E-mail:15063831558@163.com

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摘要： 摘要： 目的 探讨散发性乳腺癌中 DNA 甲基转移酶 （DNMT） 3a、 DNMT3b 蛋白表达情况及其与雌激素受体 （ER） α基因启动子甲基化状态及蛋白表达的关系。方法 选取 180 例散发性乳腺癌与 30 例乳腺纤维腺瘤组织， 采用免疫组化法检测组织中 DNMT3a、 DNMT3b 蛋白的表达情况， 甲基化特异性 PCR 检测 97 例散发性乳腺癌中 ERα基因启动子的甲基化状态。结果 乳腺纤维腺瘤与乳腺癌组织中的 DNMT3a、 DNMT3b 蛋白阳性表达率差异无统计学意义； Ⅲ~Ⅳ期乳腺癌组织的 DNMT3a、 DNMT3b 水平高于Ⅰ~Ⅱ期， 有淋巴结转移者的 DNMT3a 表达水平高于无淋巴结转移者 （均 P＜0.05）； 97 例乳腺癌中有 39 例 （40.2%） 发生 ERα基因启动子甲基化， DNMT3a 蛋白阳性表达与 ERα 基因甲基化呈正相关(rs=0.250)； DNMT3a 蛋白表达对患者的总体生存期（OS）有显著影响（P=0.035）， 对无病生存期（DFS）无明显影响（P=0.064）， DNMT3b 蛋白表达对患者的 OS 和 DFS 无影响（P 分别为 0.914、 0.961）。结论 DNMT3a、 DNMT3b 阳性表达与乳腺癌侵袭转移、 病程进展、 预后相关； DNMT3a 与 ERα基因启动子甲基化状态呈正相关； 抑制 DNMT3a、 DNMT3b 蛋白可能有利于散发性乳腺癌的预防和治疗。

关键词: 散发性乳腺癌, DNMT3a, DNMT3b, ERα, DNA 甲基化, 启动区 （遗传学）

Abstract: Abstract： Objective To investigate the correlationship between DNMT3a, DNMT3b protein expressions and the state of promoter methylation of ERα gene and ERα protein expression in the development of sporadic breast cancer. Methods A total of 180 patients with sporadic breast cancer and 30 patients with breast fibroadenoma were included in this study. The expressions of DNMT3a and DNMT3b protein were detected by immunohistochemical method. The state of promoter methyla⁃ tion of ERα gene was detected by methylation specific PCR in 97 patients with sporadic breast cancer. Results There were no significant differences in positive expression rates of DNMT3a and DNMT3b protein between breast fibroadenoma and breast cancer. There were higher expression levels of DNMT3a and DNMT3b in breast cancer patient of Ⅲ~Ⅳ stages than those ofⅠ~Ⅱstages. The expression of DNMT3a was significantly higher in patients with lymph node metastasis than that of patients without lymph node metastasis (P < 0.05). Of 97 cases of breast cancer patients, ERα gene promoter methylation oc⁃ curred in 39 cases (40.2%). The positive expression of DNMT3a protein was positively correlated with the ERα gene methyla⁃ tion (rS=0.250). The DNMT3a protein expression showed a significant influence to the overall survival (OS) in patients of breast cancer (P=0.035), no significant influence to the disease-free survival (DFS) (P=0.064). DNMT3b protein expression showed no significant influence to OS and DFS of patients with breast cancer (P = 0.914 and 0.961). Conclusion The posi⁃ tive expressions of DNMT3a and DNMT3b are correlated with the invasion, metastasis and poor prognosis of sporadic breast cancer. DNMT3a was positively correlated with the state of ERα gene promoter methylation. The inhibition of DNMT3a and DNMT3b may have advantages in the prevention and treatment of sporadic breast cancer.

Key words: sporadic breast cancer, DNMT3a, DNMT3b, ERα, DNA methylation, promoter regions (genetics)