Analysis of estrogen‐responsive finger protein expression in benign and malignant human breast
Analysis of estrogen‐responsive finger protein expression in benign and malignant human breast
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人乳腺良恶性雌激素响应指状蛋白表达分析
DOI：
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发表时间：
2001
影响因子：
6.4
通讯作者：
R. Coombes
中科院分区：
文献类型：
--
作者：
Simon D. Thomson;Simak Ali;L. Pickles;Jacqueline Taylor;P. Pace;M. Lymboura;S. Shousha;R. Coombes
雌激素反应指蛋白（EFP）基因最初是在基因组DNA中筛选含有雌激素反应元件（ERE）的基因时发现的，随后发现其表达受雌激素调节，并与小鼠雌激素受体（ER）α阳性组织相关。人类染色体定位将其定位于17q23.1，靠近BRCA1，在乳腺癌中经常丢失的区域。结构相关的蛋白质已被牵连在各种重要的细胞过程，包括致癌。鉴于ER在大部分乳腺癌中过度表达，我们推断EFP可能在介导乳腺癌的雌激素依赖性进展中发挥作用。我们提出了抗EFP的血清，并表明EFP存在于乳腺细胞系和正常乳腺组织上皮细胞的细胞质中。此外，EFP存在于细胞培养基中，表明它可能是分泌的。石蜡包埋乳腺活检标本的免疫组织化学显示，与正常乳腺相比，泌乳期乳腺和纤维腺瘤中的EFP水平显著更高（分别为p < 0.001和p = 0.001），这可能是雌激素反应性的结果。乳腺癌中的水平降低（p = 0.02），与其他免疫组化、组织病理学或临床数据无关。肿瘤EFP和ER状态之间缺乏相关性可能表明逃避雌激素控制，指出肿瘤发病机制的新模型。泌乳期乳腺中EFP水平的增加和恶性肿瘤的减少表明EFP在促进乳腺分化中的作用。© 2001 Wiley利斯公司
The estrogen‐responsive finger protein (EFP) gene was originally identified in a screen of genomic DNA for genes containing estrogen‐response elements (EREs), and its expression was subsequently shown to be estrogen‐regulated and correlated with estrogen receptor (ER)α‐positive tissues in mice. Human chromosomal mapping localized it to 17q23.1, close to BRCA1, in a region frequently lost in breast cancers. Structurally related proteins have been implicated in a variety of important cellular processes, including carcinogenisis. Given that ER is over‐expressed in a large proportion of breast cancers, we reasoned that EFP may play a role in mediating the estrogen‐dependent progression of breast cancer. We raised anti‐sera to EFP and show that EFP is present in the cytoplasm in mammary cell lines and epithelial cells of normal breast tissue. Furthermore, EFP is present in cell culture medium, suggesting that it may be secreted. Immunohistochemistry of paraffin‐embedded breast biopsy specimens showed significantly greater levels of EFP in lactating breast and fibroadenomata compared to normal breast (p < 0.001 and p = 0.001, respectively), which is likely to be a result of estrogen responsiveness. Levels were reduced in breast cancer (p = 0.02), where no correlation was seen with other immunohistochemical, histopathological or clinical data. The lack of correlation between EFP and ER status of tumors could indicate escape from estrogenic control, pointing to new models of tumor pathogenesis. Increased levels of EFP in lactating breast and the reduction in malignancy suggest a role for EFP in promoting mammary gland differentiation. © 2001 Wiley‐Liss, Inc.
影响因子：
56.9
作者：
Parks, DJ;Blanchard, SG;Lehmann, JM
通讯作者：
Lehmann, JM