Activation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage
Activation of the thromboxane A2 pathway in human prostate cancer correlates with tumor Gleason score and pathologic stage
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DOI：
10.1016/j.eururo.2006.01.036
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发表时间：
2006-11-01
期刊：
影响因子：
23.4
通讯作者：
Waltregny, David
中科院分区：
文献类型：
--
作者：
Dassesse, Thibaut;de Leval, Xavier;Waltregny, David
目的：探讨血栓素A(2) （TXA(2)）通路在人前列腺癌（PCa）中的潜在作用。方法：对46例人前列腺癌组织切片中TXA2通路的主要参与者环氧化酶-2 （COX-2）、TXA2合成酶（TXS）和TXA(2)受体（TPRs）的表达进行分析。结果：COX-2、TXS、TPRs在恶性前列腺上皮细胞中的表达水平明显高于相应的非肿瘤前列腺上皮细胞。在高级别前列腺上皮内瘤变（HGPIN）腺体中也观察到这些抗原的免疫反应性增加。COX-2、TXS和TPR蛋白通常在前列腺癌病变中表现出协调的过表达模式，通过一系列组织切片进行评估。肿瘤中这些蛋白水平的升高均与较高的Gleason评分和病理分期显著相关。结论：与TXA2通路相关的蛋白在人前列腺癌中表达上调，其表达水平与肿瘤前列腺外扩张和分化丧失有关。我们的研究首次同时检测了该通路中包括TXA2受体在内的所有关键蛋白，结果表明TXA2通路可能是PCa预防/治疗的潜在靶点。(c) 2006年欧洲泌尿外科协会。Elsevier B.V.版权所有。
Objective: We investigated the potential involvement of the thromboxane A(2) (TXA(2)) pathway in human prostate cancer (PCa).Methods: Expression of cyclooxygenase-2 (COX-2), TXA2 synthase (TXS), and TXA(2) receptors (TPRs), the main actors of the TXA2 pathway, was analyzed on serial tissue sections from 46 human PCa specimens.Results: The expression levels of COX-2, TXS, and TPRs were significantly higher in malignant than in corresponding nontumoral prostatic epithelial cells. Increased immunoreactivity for these antigens was also observed in high-grade prostate intraepithelial neoplasia (HGPIN) glands. COX-2, TXS, and TPR proteins usually displayed a coordinated overexpression pattern in PCa lesions, as assessed in serial tissue sections. Increased levels of these proteins in the tumors were all significantly associated with higher Gleason scores and pathologic stages.Conclusions: Proteins specifically involved in the TXA2 pathway are up-regulated in human PCa and their level of expression is associated with tumor extraprostatic extension and loss of differentiation. our study is the first to examine simultaneously all key proteins involved in this pathway including TXA2 receptors and results suggest that the TXA2 pathway may be a potential target for PCa prevention/therapy. (c) 2006 European Association of Urology. Published by Elsevier B.V. All rights reserved.