Breast tumors that overexpress nuclear metastasis-associated 1 (MTA1) protein have high recurrence risks but enhanced responses to systemic therapies
Breast tumors that overexpress nuclear metastasis-associated 1 (MTA1) protein have high recurrence risks but enhanced responses to systemic therapies
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DOI：
10.1007/s10549-005-9016-8
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发表时间：
2006-01-01
影响因子：
3.8
通讯作者：
O'Connell, P
中科院分区：
文献类型：
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作者：
Martin, MD;Hilsenbeck, SG;O'Connell, P
核转移相关蛋白 1 (MTA1) 是一种雌激素受体共阻遏蛋白，通过染色质重塑调节转录，相对于非转移性肿瘤，MTA1 信使核糖核酸 (mRNA) 水平在几种局部晚期和转移性肿瘤中升高。我们实验室之前的研究将 MTA1 映射到一个区域，该区域显示出与淋巴结阴性肿瘤相比，转移的原发性乳腺癌中 LOH（杂合性丢失）显着降低，这表明 MTA1 的表观遗传改变会影响转移潜力。本研究检查了治疗和未治疗的原发性人类乳腺癌中 MTA1 蛋白的免疫组织化学表达，以研究 MTA1 表达与临床结果之间的关系。过度表达 MTA1 蛋白的淋巴结阴性肿瘤与淋巴结阳性肿瘤具有相似的复发风险。在未经治疗的淋巴结阴性肿瘤的多变量分析中，MTA1 的最高表达与复发风险增加相关（多变量分析的风险比 (HR)=2.72，p=0.0003）。他莫昔芬和/或蒽基化疗消除了所有 MTA1 与临床结果的关联，表明 MTA1 过度表达可预测早期疾病复发，但会使乳腺肿瘤对全身治疗敏感。
Nuclear metastasis-associated 1(MTA1) protein is an estrogen receptor co-repressor that regulates transcription via chromatin remodeling, and MTA1 messenger ribonucleic acid (mRNA) levels are elevated in several kinds of locally advanced and metastatic tumors relative to non-metastatic tumors. Previous studies in our laboratory mapped MTA1 into a region showing significantly lower LOH (loss of heterozygosity) in primary breast cancers with metastases compared to node-negative tumors, suggesting that epigenetic alterations of MTA1 affect metastatic potential. The present study examined immunohistochemical expression of the MTA1 protein in treated and untreated primary human breast cancers to study the relationship between MTA1 expression and clinical outcome. Node-negative tumors that overexpress MTA1 protein had recurrence risks similar to node-positive tumors. In multivariate analysis of untreated node-negative tumors, highest expression of MTA1 was associated with increased relapse risk (hazard ratio (HR)=2.72, p=0.0003 for multivariate analysis). Tamoxifen and/or anthracylcene-based chemotherapies eliminated all MTA1 associations with clinical outcome, suggesting MTA1 overexpression predicts early disease relapse, but sensitizes breast tumors to systemic therapies.