MAGE-D4B is a novel marker of poor prognosis and potential therapeutic target involved in breast cancer tumorigenesis
MAGE-D4B is a novel marker of poor prognosis and potential therapeutic target involved in breast cancer tumorigenesis
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DOI：
10.1002/ijc.26200
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发表时间：
2012-05-01
影响因子：
6.4
通讯作者：
O'Driscoll, Lorraine
中科院分区：
文献类型：
--
作者：
Germano, Serena;Kennedy, Susan;O'Driscoll, Lorraine
黑色素瘤相关抗原(MAGE)家族成员通常被描述为肿瘤特异性抗原。MAGE-D4B与乳腺癌之间的联系尚未被报道，编码蛋白的功能作用也从未被确定。我们对104个浸润性乳腺肿瘤进行了微阵列分析，并与非癌乳腺活检组织进行了匹配。定量聚合酶链式反应在一个独立的生物库中用于验证。为了探讨MAGE-D4B在乳腺肿瘤发生中的生物学意义，我们在体外评价了MAGE-D4B的表型效应。总体而言，在43%的肿瘤中检测到MAGE-D4B，而在正常乳腺组织中未检测到。MAGE-D4B被发现与肿瘤进展相关，在无复发和总生存期方面是预后不良的独立指标，与化疗反应有潜在的预测相关性。RNA干扰介导的MAGE-D4B基因敲除通过影响非锚定生长、黏附、迁移和侵袭，影响非黏附生长、黏附、迁移和侵袭，并通过调控侵袭抑制基因E-钙粘蛋白的表达，显著抑制Hs578T细胞的侵袭特性。
Melanoma-associated antigen (MAGE) family members are generally described as tumor-specific antigens. An association between MAGE-D4B and breast cancer has yet to be reported and the functional role of the encoded protein has never been established. We performed microarray analysis of 104 invasi ve breast tumors and matched non-cancerous breast biopsies. qPCR wasused for validation in an independent biobank. To investigate the biological relevance of MAGE-D4B in breast tumorigenesis, its phenotypic effects were assessed in vitro. Overall, MAGE-D4B was detected in 43% of tumors while undetected in normal breast tissue. MAGE-D4B was found to correlate with tumor progression and to be an independent prognostic marker for poor outcome in term of relapse-free and overall survival, with potential predictive relevance in relation to response to chemotherapy. RNA interference-mediated knockdown of MAGE-D4B significantly hampered the invasive properties of Hs578T cells by affecting anchorage-independent growth, adhesion, migration and invasion affecting anchorage-independent growth, adhesion, migration and invasion and by modulating expression of invasion-suppressor gene E-cadherin.