Mao Xiao-yun, Chen Hao, Wang Huan, Wei Jing, Liu Chong, Zheng Hua-chuan, Yao Fan, Jin Feng
Department of Breast Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning, 110001, People's Republic of China.
Tumour Biol. 2012 Oct;33(5):1565-72. doi: 10.1007/s13277-012-0410-7. Epub 2012 May 29.
Metastasis tumor antigen 1 (MTA1), a novel candidate metastasis-associated gene, is known to increase the migration and invasion of various tumor cells in vitro. It also plays an important role in tumorigenesis and tumor aggressiveness of breast cancer. Estrogen receptor alpha (ERα) plays an important role in the etiology of breast cancer and has been widely accepted as a prognostic marker for breast cancer and a response predictor for endocrine therapy. The ERα gene methylation has been linked to the lack of ERα expression in breast cancer. The aim of the study is to assess the correlation between the ERα methylation and MTA1 expression in breast cancer and further to investigate whether the repressed ERα methylation can downregulate the expression of MTA1 in vitro. In general, we found ERα methylation had significant correlation with the MTA1 expression (p < 0.05) in female patients of breast cancer (n = 102) by methylation-specific polymerase chain reaction and immunohistochemistry. To gain a deeper insight into the molecular mechanism underlying the relation between MTA1 and ERα methylation, we treated the invasive breast cancer cell lines with the demethylating agent, found the downregulation of MTA1 protein expression, and mRNA with the unmethylation of ERα (p < 0.05). And the invasive ability of breast cancer cells was significantly positively associated with MTA1 expression. These unique findings have greatly extended our current knowledge about the relation between ERα methylation and MTA1 expression. These data strongly support the hypothesis that methylation is involved in the relation between MTA1 and ERα in breast cancer.
转移瘤抗原1(MTA1)是一种新型的候选转移相关基因,已知其可在体外增强各种肿瘤细胞的迁移和侵袭能力。它在乳腺癌的肿瘤发生和肿瘤侵袭性中也起着重要作用。雌激素受体α(ERα)在乳腺癌的病因学中发挥重要作用,并且已被广泛接受为乳腺癌的预后标志物和内分泌治疗的反应预测指标。ERα基因甲基化与乳腺癌中ERα表达的缺失有关。本研究的目的是评估乳腺癌中ERα甲基化与MTA1表达之间的相关性,并进一步研究在体外抑制ERα甲基化是否能下调MTA1的表达。总体而言,我们通过甲基化特异性聚合酶链反应和免疫组织化学发现,在102例女性乳腺癌患者中,ERα甲基化与MTA1表达存在显著相关性(p<0.05)。为了更深入地了解MTA1与ERα甲基化之间关系的分子机制,我们用去甲基化剂处理侵袭性乳腺癌细胞系,发现随着ERα去甲基化,MTA1蛋白表达和mRNA水平下调(p<0.05)。并且乳腺癌细胞的侵袭能力与MTA1表达显著正相关。这些独特的发现极大地扩展了我们目前对ERα甲基化与MTA1表达之间关系的认识。这些数据有力地支持了甲基化参与乳腺癌中MTA1与ERα之间关系的假说。