孕酮受体亚型在脑膜瘤中的表达。

PubMed ID
发表日期 2001年Aug月

原始出处 欧洲癌症杂志(牛津,英格兰:1990)
European journal of cancer (Oxford, England : 1990)
作者 Verheijen  F M  Sprong  M  Jacobs  H M  Donker  G H  Amelink  G J  Thijssen  J H  Blankenstein  M A 

文献标题 孕酮受体亚型在脑膜瘤中的表达。
Progesterone receptor isoform expression in human meningiomas.

文献摘要

大多数脑膜瘤表达孕酮受体(PR),因此脑膜瘤被认为是孕酮反应性的。此外,PR与预后的关系也有报道。至少存在两种PR亚型,PR-B(116-120 kDa)和PR-A(81 kDa),它们可能具有不同的生物学功能。了解这两种异构体的差异表达对于理解孕酮对脑膜瘤生长的影响是必要的。因此,本研究采用免疫印迹法检测了61例脑膜瘤中PR-A和PR-B的表达水平。总PR表达水平用配体结合试验(LBA)测定。PR亚型和pr78kda蛋白(PR-78)在脑膜瘤中均有表达。PR-A表达高于PR-B的脑膜瘤总PR(LBA)水平显著升高(P<0.001)。PR-78条带强度与PR-B条带强度呈负相关(r(s)=-0.76,P<0.0001)。PR-78可能是一种内源性降解产物,但在PR-B和PR-78的生物发生过程中,类似的调控途径并不排除。脑膜瘤包含两种PR亚型,但比率变化很大,这种变异性可能具有一定的生物学意义。大多数脑膜瘤表达PR-A多于PR-B。因此,在脑膜瘤中,假设PR-B比PR-A更具转录活性,孕酮的反应性可能是基于靶基因的反式激活而不是反式激活,孕酮阻断可能只对某些脑膜瘤亚群有效。


The majority of meningiomas express the progesterone receptor (PR), and therefore meningiomas are considered to be progesterone-responsive. In addition, an association has been reported between PR and prognosis. At least two PR isoforms exist, PR-B (116--120 kDa) and PR-A (81 kDa), each of which are likely to have different biological functions. Knowledge of the differential expression of both isoforms is necessary to understand the effects of progesterone on meningioma growth. Therefore, in this study, PR-A and PR-B expression levels were determined in 61 human meningiomas by immunoblotting. Total PR expression levels were determined with a ligand binding assay (LBA) (total PR(LBA)). Both PR isoforms and an additional PR 78 kDa protein (PR-78) were expressed in the meningiomas. Meningiomas expressing more PR-A than PR-B had significantly higher total PR(LBA) levels (P<0.001). The PR-78 band intensity was negatively associated with that of PR-B (r(s)=-0.76, P<0.0001). PR-78 may represent an endogenous degradation product, but a similar regulation pathway in the biogenesis of both PR-B and PR-78 is not excluded. Meningiomas contain both PR isoforms, but in highly variable ratios and this variability may have some biological significance. Most meningiomas express more PR-A than PR-B. Therefore in meningioma, assuming that PR-B is more transcriptionally active than PR-A, progesterone responsiveness could be based on transrepression rather than on transactivation of target genes, and progesterone blockade may only be effective in certain subsets of meningiomas.


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