Auto-regulation of the estrogen receptor promoter
Auto-regulation of the estrogen receptor promoter
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DOI：
10.1016/s0960-0760(97)00023-x
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发表时间：
1997-06-01
影响因子：
4.1
通讯作者：
Fuqua, SAW
中科院分区：
文献类型：
--
作者：
Castles, CG;Oesterreich, S;Fuqua, SAW
雌激素受体（ER）的存在与否在乳腺肿瘤的诊断和治疗中起着关键作用。已知er阳性的乳腺肿瘤患者预后较好。这样的观察结果使我们开始探索是什么导致一些乳腺肿瘤过度表达雌激素受体而另一些肿瘤表达水平很低或根本不表达雌激素受体。为了开始研究内质网调控，我们首先选择检查位于人类内质网基因转录序列上游的内质网启动子的200 bp区域。我们发现，瞬时转染ER阴性HeLa细胞时，ER启动子的这一区域具有基础活性。通过共转染野生型ER表达载体，ER启动子活性进一步增加，并且这种增加的活性依赖于激素。几种ER缺失突变体结构也能够增加ER启动子片段的活性，但没有一种结构能够像全长ER那样支持等效活性。因此，我们得出结论，内质网可以促进其自身的表达，我们假设这种自我调节可能有助于其在某些乳腺肿瘤中的过度表达。1997爱思唯尔科学有限公司
The presence or absence of estrogen receptor (ER) plays a key role in the diagnosis and treatment of breast tumors. It is known that patients with breast tumors classified as ER-positive have a better prognosis. Observations such as this have led us to explore the question of what makes some breast tumors overexpress ER whereas others express either very low levels or none at all. To begin a study of ER regulation, we first chose to examine a 200 bp region of the ER promoter located immediately upstream from the transcribed sequence of the human ER gene. We found that this region of the ER promoter contained basal activity when transiently transfected into ER-negative HeLa cells. ER promoter activity was further increased by co-transfection of a wild-type ER expression vector, and this increased activity was hormone-dependent, Several ER deletion mutant constructs were also able to increase the activity of the ER promoter fragment, but none could support equivalent activity as was seen with the full-length ER. Therefore, we conclude that the ER can contribute to its own expression, and we hypothesize that this auto-regulation may contribute to its overexpression in some breast tumors. (C) 1997 Elsevier Science Ltd.