Sp1 is essential for estrogen receptor α gene transcription
Sp1 is essential for estrogen receptor α gene transcription
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DOI：
10.1016/s0960-0760(02)00151-6
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发表时间：
2002-09-01
影响因子：
4.1
通讯作者：
Fuqua, SAW
中科院分区：
文献类型：
--
作者：
deGraffenried, LA;Hilsenbeck, SG;Fuqua, SAW
调节乳腺肿瘤雌激素受体（ER）a表达的确切分子机制尚不清楚，但研究表明，这种调节至少部分是转录的。因此，我们进行了详细的分析ER α启动子活性在一些乳腺癌细胞系。我们发现ER α启动子活性的大部分位于该基因5 '侧翼区的前245 bp内。在瞬时反式激活试验中，使用连接子扫描仪突变分析，在-245至-192区域内鉴定了对完整ER α启动子转录活性至关重要的三个元件。这三个元件包括转录因子Sp1家族的两个结合位点以及非共有E盒。我们表明，SP1和温泉绑定到这个区域使用电泳迁移率变动分析。在Sp1/3阴性的果蝇Schneider SL 2细胞中外源表达Sp1或Spa导致ER α启动子的-245至+212bp片段的反式激活。这些数据表明ER α的转录依赖于Spl家族成员的表达。(C)2002年由Elsevier Science Ltd.出版
The exact molecular mechanisms regulating estrogen receptor (ER)a expression in breast tumors are unclear, but studies suggest that the regulation is at least partly transcriptional. We therefore undertook a detailed analysis of ERalpha promoter activity in a number of breast cancer cell lines. We find that the majority of ERalpha promoter activity lies within the first 245 by of the 5'-flanking region of the gene. Three elements essential for full ERa promoter transcriptional activity were identified within the -245 to -192 by region in transient transactivation assays using linker-scanner mutation analysis. These three elements include two binding sites for the Sp1 family of transcription factors as well as a non-consensus E box. We show that both Sp1 and Spa bind to this region using electrophoretic mobility shift assays. Exogenous expression of Sp1 or Spa in Sp1/3-negative Drosophila Schneider SL2 cells results in transactivation of the -245 to +212bp fragment of the ERa promoter. These data demonstrate that transcription of ERa is dependent upon the expression of members of the Spl family. (C) 2002 Published by Elsevier Science Ltd.