Tumor Biol：MTA1表达与乳腺癌ER-α甲基化

肿瘤转移相关基因家族是近年发现的由某些肿瘤转移相关基因及其编码产物组成的家族,而作为该家族中首个被发现的基因,转移性肿瘤抗原1（metastatic tumor antigen 1，MTA1）基因在多种恶性肿瘤中过度表达，并且与人类肿瘤的恶性特征密切相关。

MTA1基因在乳腺的激素调控和乳腺癌的发生、发展中都起到了重要的作用，因此MTA1基因及其编码蛋白的检测可能成为乳腺癌新的临床预后指标和治疗靶点。

转移肿瘤抗原1（MTA1）是一个潜在的转移相关候选基因，在体外，MTA1的增加导致各种类型肿瘤细胞的迁移和侵袭增加。此外，MTA1还在肿瘤的发生和侵袭性乳腺癌肿瘤中起着重要作用。

雌激素受体α（甲型雌激素受体）在乳腺癌发病中扮演重要作用，已被广泛证实是乳腺癌的预后指标。近日，Tumor Biology杂志上的一则研究评估了雌激素受体甲型甲基化和MTA1表达在乳腺癌中的作用，进一步研究分析抑制雌激素受体甲型甲基化是否可以下调MTA1的表达。聚合酶链反应和免疫组化研究发现，乳腺癌女性患者中雌激素受体甲型甲基化与MTA1表达甲基化特异性有显著相关性。这些数据有力地支持了甲基化参与乳腺癌MTA1和雌激素受体甲型之间的相互作用。

doi:10.1007/s13277-012-0410-7
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MTA1 expression correlates significantly with ER-alpha methylation in breast cancer

Xiao-yun Mao, Hao Chen, Huan Wang, Jing Wei, Chong Liu, Hua-chuan Zheng, Fan Yao and Feng Jin

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.