ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas.
ER-alpha36, a novel variant of ER-alpha, is expressed in ER-positive and -negative human breast carcinomas.
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发表时间：
2008
影响因子：
2
通讯作者：
L. Lee;Jiang Cao;Hao Deng;Ping Chen;Z. Gatalica;Zhaoyi Wang
中科院分区：
文献类型：
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作者：
L. Lee;Jiang Cao;Hao Deng;Ping Chen;Z. Gatalica;Zhaoyi Wang
背景雌激素受体α（ER-α）的表达状态是乳腺癌诊断和预后的重要指标之一。ER-α是一种66 kDa的配体诱导的转录因子，其特征是通过免疫组织化学（IHC）在乳腺癌标本的细胞核中检测到。最近，我们鉴定并克隆了ER-α的36-kDa新变体ER-α 36，其缺乏反式激活结构域，并且作为全长ER-α（ER-α 66）和ER-β的反式激活活性的显性负效应物发挥功能。ER-α 36主要定位于细胞质和质膜，并通过转导膜启动的信号级联反应对雌激素和抗雌激素进行应答，刺激增殖并可能导致乳腺癌中更具侵袭性的表型。ER-α 36在已建立的ER阳性和阴性乳腺癌细胞系中表达。然而，其在乳腺癌标本中的表达和定位尚未得到评估。由于ER-α 36可能在乳腺癌肿瘤发生中起重要作用，因此除了ER-α 66的表达模式之外，还检查ER-α 36的表达模式对于乳腺癌的更全面的分子谱分析具有临床重要性。患者和方法通过IHC评估31例乳腺癌患者组织的ER-α 36和ER-α 66蛋白表达状态，并使用ER-α 66或ER-α 36特异性抗体通过Western印迹分析分析另外6例患者组织样品。结果：我们的实验揭示了ER-α 36在ER-α 66阳性和阴性乳腺癌样本中的细胞质和质膜相关表达模式。此外，ER-α 36表达似乎与细胞核和/或细胞质ER-α 66表达降低相关，提示其作为诊断和预后标志物的潜在用途。结论ER-α 36是ER-α的一种新亚型，在ER-α 66阴性的恶性肿瘤中频繁表达，检测ER-α 36可能为更好的诊断和预后提供新的信息。
BACKGROUND The status of estrogen receptor-alpha (ER-alpha) expression is one of the most important diagnostic and prognostic factors of breast cancer. ER-alpha is a 66-kDa, ligand-induced transcription factor, characteristically detected in the cell nucleus by immunohistochemistry (IHC) in breast cancer specimens. Recently, we identified and cloned a 36-kDa novel variant of ER-alpha, ER-alpha36, which lacks both transactivation domains and functions as a dominant-negative effector of transactivation activities of the full-length ER-alpha (ER-alpha66) and ER-beta. ER-alpha36 primarily localizes to the cytoplasm and plasma membrane, and responds to both estrogens and antiestrogens by transducing membrane-initiated signaling cascades, stimulating proliferation and possibly contributing to a more aggressive phenotype in breast carcinomas. ER-alpha36 is expressed in established ER-positive and -negative breast cancer cell lines. However, its expression and localization in breast cancer specimens have not been evaluated. As ER-alpha36 may play important roles in breast cancer tumorigenesis, it is of clinical importance to examine the expression pattern of ER-alpha36, in addition to that of ER-alpha66, for more comprehensive molecular profiling of breast carcinomas. PATIENTS AND METHODS Thirty-one breast cancer patient tissues were evaluated for ER-alpha36 and ER-alpha66 protein expression status by IHC and six additional patient tissue samples were analyzed by Western blot analysis using antibodies specific to ER-alpha66 or ER-alpha36. RESULTS Our experiments reveal a cytoplasmic and plasma-membrane-associated expression pattern of ER-alpha36 in both ER-alpha66-positive and -negative breast cancer samples. Furthermore, ER-alpha36 expression appears to be associated with decreasing nuclear and/or cytoplasmic ER-alpha66 expression, suggesting its potential use as a diagnostic and prognostic marker. CONCLUSION ER-alpha36 is a novel isoform of ER-alpha, frequently expressed in ER-alpha66-negative cancers, whose detection may provide additional information for better diagnosis and prognosis.