The steroid receptor RNA activator protein is expressed in breast tumor tissues
The steroid receptor RNA activator protein is expressed in breast tumor tissues
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DOI：
10.1002/ijc.21425
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发表时间：
2006-02-15
影响因子：
6.4
通讯作者：
Leygue, E
中科院分区：
文献类型：
--
作者：
Chooniedass-Kothari, S;Hamedani, MK;Leygue, E
类固醇受体RNA激活因子（steroid receptor RNA activator，SRA）最初被描述为第一个能够特异性共激活类固醇受体活性的功能性非编码RNA。我们先前证明了乳腺癌细胞系中存在新的SRA亚型，与第一个克隆的SRA RNA相反，编码236个氨基酸的蛋白质SRAP。为了研究编码SRA RNA和SRAP表达对乳腺癌进展的可能影响，我们通过Western印迹分析检测了74例随后用他莫昔芬治疗的原发性乳腺肿瘤患者。原发性肿瘤SRAP表达阳性的患者（n = 24）死于复发性疾病的可能性显著低于SRAP阴性患者（n = 50）（Kaplan-Meier生存曲线p = 0.047）。我们通过在雌激素受体阳性的MCF-7乳腺癌细胞系中稳定过表达SRAP产生了2个细胞系，SRAP-V5-High. A和SRAP-V5-High.B。瞬时转染实验，使用荧光素酶报告基因的雌激素反应元件的控制下进行，显示降低敏感性雌二醇，但没有额外的敏感性，他莫昔芬SRAP过表达细胞。总体而言，我们的数据表明，编码SRA RNA及其相应的SRAP的存在下修改乳腺癌细胞中雌激素受体的活性，SRAP可能是一种新的乳腺癌临床标志物。需要进一步的研究来确定各自的作用机制以及SRA RNA和蛋白在乳腺肿瘤发生和肿瘤进展中的作用。(c)2005年威利-利斯，hic。
The steroid receptor RNA activator (SRA) was originally described as the first functional non-coding RNA able to specifically coactivate the activity of steroid receptors. We previously demonstrated the existence in breast cancer cell lines of new SRA isoforms that, as opposed to the first cloned SRA RNA, encode for a 236-amino acid protein, SRAP. To investigate the possible implications of the coding SRA RNA and SRAP expression on breast cancer progression, we examined by Western blot analysis 74 primary breast tumors of patients subsequently treated with tamoxifen. Patients whose primary tumors were positive for SRAP expression (n = 24) had a significantly (Kaplan-Meier survival curve p = 0.047) lower likelihood of dying from recurrent disease than SRAP-negative patients (n = 50). We generated 2 cell lines, SRAP-V5-High.A and SRAP-V5-High.B, by stably over-expressing SRAP in the estrogen receptor-positive MCF-7 breast cancer cell line. Transient transfection experiments, performed using a luciferase reporter gene under the control of an estrogen-responsive element, revealed decreased sensitivity to estradiol but no additional sensitivity to tamoxifen in SRAP-overexpressing cells. Overall, our data suggest that the presence of both coding SRA RNA and its corresponding SRAP modifies the activity of estrogen receptor in breast cancer cells and that SRAP could be a new clinical marker for breast cancer. Further studies are needed to define the respective mechanisms of action and the roles of SRA RNA and protein in breast tumorigenesis and tumor progression. (c) 2005 Wiley-Liss, hic.