Okuducu Ali Fuat, Zils Ulrich, Michaelis Silke A M, Mawrin Christian, von Deimling Andreas
Institute of Neuropathology, Charite-Universitaetsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Cancer. 2006 Sep 15;107(6):1365-72. doi: 10.1002/cncr.22130.
The transcription factor avian erythroblastosis virus E26 (V-Ets) oncogene homolog 1 (Ets-1) is involved in tumor development and progression through the transcriptional regulation of several matrix-degrading enzyme systems, including matrix metalloproteinases (MMPs). It has been demonstrated that the MMPs are expressed strongly in high-grade meningiomas. To determine the biologic significance of Ets-1 in the progression of benign meningiomas, the authors investigated the expressions of Ets-1 and its target genes MMP-2 and MMP-9 in primary and recurrent, Grade 1 meningiomas.
The expression levels of Ets-1, MMP-2, and MMP-9 were examined by immunohistochemistry in 70 Grade 1 meningiomas, including 36 primary tumors without recurrence after 5 years of follow-up and 17 pairs of primary tumors and subsequent recurrences.
The results demonstrated higher expression of Ets-1, MMP-2, and MMP-9 proteins in meningiomas with subsequent recurrences compared with meningiomas from patients who had no recurrences (P < .001). In addition, Ets-1 expression was correlated with the expression of both MMP-2 and MMP-9.
Ets-1 may be involved in meningioma recurrence by up-regulating MMP-2 and MMP-9. Increased expression of these genes in World Health Organization grade 1 meningiomas may serve as an indicator for a high risk of recurrence.
转录因子禽成红细胞增多症病毒E26(V-Ets)癌基因同源物1(Ets-1)通过对包括基质金属蛋白酶(MMPs)在内的多种基质降解酶系统进行转录调控,参与肿瘤的发生和发展。已有研究表明,MMPs在高级别脑膜瘤中高表达。为了确定Ets-1在良性脑膜瘤进展中的生物学意义,作者研究了Ets-1及其靶基因MMP-2和MMP-9在原发性和复发性1级脑膜瘤中的表达情况。
采用免疫组织化学方法检测70例1级脑膜瘤中Ets-1、MMP-2和MMP-9的表达水平,其中包括36例随访5年无复发的原发性肿瘤以及17对原发性肿瘤及其随后的复发肿瘤。
结果显示,与无复发患者的脑膜瘤相比,复发性脑膜瘤中Ets-1、MMP-2和MMP-9蛋白表达更高(P <.001)。此外,Ets-1表达与MMP-2和MMP-9的表达均相关。
Ets-1可能通过上调MMP-2和MMP-9参与脑膜瘤复发。在世界卫生组织1级脑膜瘤中这些基因表达增加可能作为复发高风险的一个指标。