MTA1 expression correlates significantly with ER-alpha methylation in breast cancer
MTA1 expression correlates significantly with ER-alpha methylation in breast cancer
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MTA1 表达与乳腺癌中 ER-α 甲基化显着相关
DOI：
10.1007/s13277-012-0410-7
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发表时间：
2012-10-01
期刊：
影响因子：
--
通讯作者：
Jin，Feng
中科院分区：
文献类型：
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作者：
Mao，Xiao-yun;Chen，Hao;Jin，Feng
转移瘤抗原1 （Metastasis tumor antigen 1, MTA1）是一种新的候选转移相关基因，在体外可增加多种肿瘤细胞的迁移和侵袭。它在乳腺癌的肿瘤发生和肿瘤侵袭中也起着重要作用。雌激素受体α (Estrogen receptor α, ERα)在乳腺癌的病因学中起着重要作用，已被广泛认为是乳腺癌的预后标志物和内分泌治疗的反应预测因子。ERα基因甲基化与乳腺癌中ERα表达缺失有关。本研究旨在评估乳腺癌组织中ERα甲基化与MTA1表达的相关性，并进一步探讨ERα甲基化抑制是否能下调MTA1的体外表达。总的来说，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，ERα甲基化与MTA1在女性乳腺癌患者（n= 102）中的表达有显著相关性（p< 0.05）。为了深入了解MTA1与ERα甲基化关系的分子机制，我们用去甲基化剂处理浸润性乳腺癌细胞株，发现MTA1蛋白表达下调，mRNA表达下调与ERα非甲基化（p< 0.05）。乳腺癌细胞的侵袭能力与MTA1表达呈显著正相关。这些独特的发现极大地扩展了我们目前关于ERα甲基化和MTA1表达之间关系的知识。这些数据有力地支持了甲基化参与乳腺癌中MTA1和ERα之间关系的假设。
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.