Carroll R S, Brown M, Zhang J, DiRenzo J, Font De Mora J, Black P M
Neurosurgical Laboratories, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Clin Cancer Res. 2000 Sep;6(9):3570-5.
The predominance of meningiomas in females, their accelerated growth during the luteal phase of the menstrual cycle and during pregnancy, and the association between meningiomas and breast cancer have led to a number of studies examining the potential role of steroids on the growth of meningiomas. There are numerous discrepancies in the literature about the mitogenic effects of steroids on meningiomas in both in vitro and in vivo models. The aim of this study was to examine the expression of three steroid receptor coactivators, along with progesterone receptor and estrogen receptor in meningiomas. This additional regulatory layer may explain the heterogeneity of hormone responses observed in these tumors. Using Western blot analysis and immunohistochemistry, we demonstrate the expression of the steroid coactivators steroid receptor cofactor (SRC-1), amplified in breast cancer protein (AIB1), and transcriptional intermediary factor 2 (TIF2) in 81, 76, and 76% of meningiomas, respectively. The expression of SRC-1 and TIF2 is significantly related to progesterone but not to estrogen receptor expression. In contrast, seven normal brain specimens were positive for TIF2 and SRC-1 but negative for AIB1. One leptomeningeal specimen was positive for AIB1, SRC-1, and progesterone receptor. The differential expression of steroid receptor coactivators may explain the differential response of these tumors to hormonal therapy.
脑膜瘤在女性中占优势,在月经周期的黄体期和怀孕期间生长加速,以及脑膜瘤与乳腺癌之间的关联,导致了多项研究探讨类固醇对脑膜瘤生长的潜在作用。关于类固醇在体外和体内模型中对脑膜瘤的促有丝分裂作用,文献中有许多不一致之处。本研究的目的是检测三种类固醇受体共激活因子以及脑膜瘤中孕激素受体和雌激素受体的表达。这一额外的调节层可能解释了在这些肿瘤中观察到的激素反应的异质性。使用蛋白质印迹分析和免疫组织化学,我们分别在81%、76%和76%的脑膜瘤中证实了类固醇共激活因子类固醇受体辅因子(SRC-1)、乳腺癌扩增蛋白(AIB1)和转录中介因子2(TIF2)的表达。SRC-1和TIF2的表达与孕激素显著相关,但与雌激素受体表达无关。相比之下,7个正常脑标本TIF2和SRC-1呈阳性,但AIB1呈阴性。1个软脑膜标本AIB1、SRC-1和孕激素受体呈阳性。类固醇受体共激活因子的差异表达可能解释了这些肿瘤对激素治疗的不同反应。