Koehorst S G, Cox J J, Donker G H, Lopes da Silva S, Burbach J P, Thijssen J H, Blankenstein M A
Department of Endocrinology, Academic Hospital Utrecht, Netherlands.
Mol Cell Endocrinol. 1994 May;101(1-2):237-45. doi: 10.1016/0303-7207(94)90240-2.
An alternatively spliced mRNA coding for a variant estrogen receptor (ER) missing exon 4 (ERdelta4) was detected in the breast tumor cell line MCF7 and meningioma tissue by using the reversed transcriptase PCR technique. The trans-activational properties of this mutant ER were assessed in embryo carcinoma P19EC and human choriocarcinoma JEG3 cells by co-transfection of the ERdelta4 expression vector with an oxytocin promoter construct containing an estrogen-responsive element. ERdelta4 did not trans-activate the oxytocin promoter in either a hormone-dependent or -independent manner. Co-transfection of ERdelta4 together with the wtER did not show any interference of ERdelta4 on the stimulation of the oxytocin promoter by the wtER. ERdelta4 was translated in vitro. Its capacity to bind estradiol, and the binding of the variant to a synthetic estrogen-responsive element were compared to those of the wild-type receptor. ERdelta4 did not bind to a synthetic estrogen-responsive element, nor did it bind estradiol. Hence, ERdelta4 appears to be a silent variant and we speculate that it is without any role in tumor progression.
通过逆转录聚合酶链反应技术，在乳腺癌细胞系MCF7和脑膜瘤组织中检测到一种编码缺失外显子4的变异雌激素受体（ER）的选择性剪接mRNA（ERdelta4）。通过将ERdelta4表达载体与含有雌激素反应元件的催产素启动子构建体共转染，在胚胎癌P19EC和人绒毛膜癌JEG3细胞中评估了这种突变型ER的反式激活特性。ERdelta4在激素依赖性或非依赖性方式下均未反式激活催产素启动子。将ERdelta4与野生型ER（wtER）一起共转染，未显示ERdelta4对wtER刺激催产素启动子有任何干扰。ERdelta4在体外进行了翻译。将其结合雌二醇的能力以及该变异体与合成雌激素反应元件的结合情况与野生型受体进行了比较。ERdelta4不与合成雌激素反应元件结合，也不结合雌二醇。因此，ERdelta4似乎是一种无活性的变异体，我们推测它在肿瘤进展中没有任何作用。
