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人脑膜瘤中孕激素受体的雌激素受体非依赖性表达——综述

Oestrogen receptor independent expression of progestin receptors in human meningioma--a review.

作者信息

Blankenstein M A, Koehorst S G, van der Kallen C J, Jacobs H M, van Spriel A B, Donker G H, van't Verlaat J W, Blaauw G, Thijssen J H

机构信息

Department of Endocrinology, Academic Hospital Utrecht, The Netherlands.

出版信息

J Steroid Biochem Mol Biol. 1995 Jun;53(1-6):361-5. doi: 10.1016/0960-0760(95)00080-j.

Abstract

Human meningiomas are rich in progestin receptors (PR), which are expressed in this tissue in an oestrogen independent fashion. In the search for an explanation of this observation, the existence of a protein in human meningioma cytosol which is capable of binding to a synthetic oestrogen responsive element (ERE) has been demonstrated. Using reverse transcriptase, PCR mRNA encoding for the wild-type oestrogen receptor (ER) was found. In addition, several splice variants of ER mRNA have been identified in human meningioma tissue, including variants lacking exons 4, 5 and 7. We found the ER delta 4 protein to have no transcriptional activity and the ER delta 7 protein reportedly is dominant negative. These mutants therefore probably are not responsible for the autonomous PR synthesis in human meningioma. The ER delta 5 protein, by contrast, has been reported to have oestrogen independent transcriptional activity and it is tempting to speculate that this protein is similar or identical to the ERE binding protein we have found in human meningioma. The role of wild type ER mRNA is presently unclear. Activation of other signal transduction pathways in meningioma does not lead to an increased PR concentration. The promoter area of the meningioma PR gene should be investigated for the possible sensitivity to other transcription factors.

摘要

人类脑膜瘤富含孕激素受体(PR),该受体在这种组织中以雌激素非依赖方式表达。为了寻找这一现象的解释,已证实在人类脑膜瘤细胞溶质中存在一种能够与合成雌激素反应元件(ERE)结合的蛋白质。利用逆转录酶,发现了编码野生型雌激素受体(ER)的PCR mRNA。此外,在人类脑膜瘤组织中还鉴定出了几种ER mRNA的剪接变体,包括缺失外显子4、5和7的变体。我们发现ERδ4蛋白没有转录活性,而据报道ERδ7蛋白具有显性负性作用。因此,这些突变体可能并非人类脑膜瘤中PR自主合成的原因。相比之下,据报道ERδ5蛋白具有雌激素非依赖转录活性,因此很容易推测该蛋白与我们在人类脑膜瘤中发现的ERE结合蛋白相似或相同。目前尚不清楚野生型ER mRNA的作用。脑膜瘤中其他信号转导途径的激活不会导致PR浓度升高。应研究脑膜瘤PR基因的启动子区域对其他转录因子的可能敏感性。

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