Liu Mengying, Zhang Kaiyuan, Zhao Yangang, Guo Qiang, Guo Deyu, Zhang Jiqiang
Department of Neurobiology, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing, 400038, China.
Tumour Biol. 2015 May;36(5):3251-61. doi: 10.1007/s13277-014-2954-1. Epub 2014 Dec 23.
Steroid receptors such as androgen receptor (AR) and estrogen receptors (ER) ER-α and ER-β, and their receptor coactivators (steroid receptor coactivator, SRC) are widely localized in the brain. Although previous studies have investigated the expression of steroid receptors in brain tumors like astrocytoma, the studies on the expression of steroid receptors and SRCs in other brain tumors are lacking. Here, we investigated the expression of AR, ERs, and SRCs in neuroepithelial (medulloblastoma, ependymoma, oligodendroglioma) and meningothelial meningioma using tissue microarray immunohistochemistry. Compared to normal brain tissue, we found that the expression of SRC-1, SRC-3, and ER-α significantly decreased in meningothelial tumor and neuroepithelial tumor, suggesting that the SRC-1/SRC-3 levels may be regulated by ER-α. Moreover, the levels of AR strongly correlated to the levels of ER-β. Furthermore, correlation was also detected between SRC-3 and AR in neuroepithelial tumor, and between ER-α and ER-β in meningothelial tumor. In addition, the decreased ratio of SRC-1/SRC-3 was associated with an increase of ER-β in neuroepithelial tumor. These results indicate that expressions of different steroid receptors and activators may be tumor type dependent. While AR, ER-α, and ER-β may be involved in the pathogenesis of meningothelial tumor, SRCs/ER-β axis and SRC-3/AR axis may play a role in the pathogenesis of neuroepithelial tumor.
类固醇受体,如雄激素受体(AR)、雌激素受体(ER)的α亚型(ER-α)和β亚型(ER-β)及其受体共激活因子(类固醇受体共激活因子,SRC)广泛分布于大脑中。尽管此前已有研究探讨类固醇受体在星形细胞瘤等脑肿瘤中的表达情况,但对于其他脑肿瘤中类固醇受体及SRCs表达的研究仍较为缺乏。在此,我们利用组织芯片免疫组化技术研究了AR、ERs和SRCs在神经上皮性肿瘤(髓母细胞瘤、室管膜瘤、少突胶质细胞瘤)和脑膜内皮型脑膜瘤中的表达。与正常脑组织相比,我们发现SRC-1、SRC-3和ER-α在脑膜内皮型肿瘤和神经上皮性肿瘤中的表达显著降低,提示SRC-1/SRC-3水平可能受ER-α调控。此外,AR水平与ER-β水平密切相关。而且,在神经上皮性肿瘤中检测到SRC-3与AR之间存在相关性,在脑膜内皮型肿瘤中检测到ER-α与ER-β之间存在相关性。另外,在神经上皮性肿瘤中,SRC-1/SRC-3比值的降低与ER-β的升高相关。这些结果表明,不同类固醇受体及激活因子的表达可能因肿瘤类型而异。AR、ER-α和ER-β可能参与脑膜内皮型肿瘤的发病机制,而SRCs/ER-β轴和SRC-3/AR轴可能在神经上皮性肿瘤的发病机制中发挥作用。