Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma
Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma
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DOI：
10.1016/j.humpath.2007.05.014
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发表时间：
2008-01-01
期刊：
影响因子：
3.3
通讯作者：
Reich, Reuven
中科院分区：
文献类型：
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作者：
Davidson, Ben;Hadar, Rivka;Reich, Reuven
本研究的目的是分析PTEN(第10号染色体缺失的磷酸酶和张力蛋白同源物)的负调控因子DJ-1在卵巢癌中的表达及其临床意义，并探讨DJ-1水平与其转录调节因子特异性蛋白1(Sp1)和特异性蛋白3(SP3)表达的关系。应用逆转录聚合酶链式反应技术检测72例胸腔积液、57例实体瘤、42例原发肿瘤和15例转移瘤组织中DJ-1信使核糖核酸(MRNA)的表达。对大部分标本(48例胸腔积液，50例实体瘤)进行Sp1和SP3mRNA的表达分析。应用免疫组织化学方法检测201例胸腔积液和92例实体瘤中PTEN蛋白的表达。DJ-1mRNA在80%以上的标本中表达，没有明显的解剖部位。DJ-1表达与积液中Sp1表达呈正相关(P=0.03)，与实体瘤中Sp1表达呈正相关(P=0.02)，与SP3表达呈正相关(P=0.002)。在积液中，治疗后DJ-1的表达高于治疗前(P=.012)。在单变量分析中，较高的DJ-1水平(P=.027)和较高的FIGO分期(IV期与III期；P=.003)与化疗后积液患者较短的无进展生存期相关。PTEN在胸腔积液和实体瘤中的表达较低(分别为23%和13%)，其表达与DJ-1水平和生存期无关。我们的数据显示，DJ-1在晚期卵巢癌的所有解剖部位都有频繁的表达，并与其转录调控因子Sp1和Sp3共表达。相反，PTEN在这种疾病中的表达很少见。这些发现可能提供了调节癌细胞存活和侵袭性的分子机制之一。(C)2008 Elsevier Inc.保留所有权利。
The aim of this study was to analyze the expression and clinical role of DJ-1, a negative regulator of PTEN (phosphatase and tensin homolog deleted on chromosome 10), in ovarian carcinoma, and investigate the putative association between DJ-1 levels and expression of its transcriptional regulators specificity protein 1 (Sp1) and specificity protein 3 (Sp3). Effusions (n = 72) and solid tumors (n = 57, 42 primary and 15 metastases) were analyzed for DJ-1 messenger RNA (mRNA) expression using reverse transcriptase-polymerase chain reaction. Most specimens (48 effusions, 50 solid tumors) were additionally analyzed for Sp1 and Sp3 mRNA expression. PTEN protein expression was analyzed in 201 effusions and 92 solid tumors using immunohistochemistry. DJ-1 mRNA was expressed in more than 80% of specimens, with no preferential anatomical site. DJ-1 expression was positively associated with Sp1 expression in effusions (P = .03) and with Spl (P = .02) and Sp3 (P = .002) expression in solid tumors. In effusions, DJ-1 expression was higher in postchernotherapy compared with prechernotherapy specimens (P = .012). Higher DJ-1 levels (P = .027) and more advanced FIGO stage (IV versus III; P = .003) correlated with shorter progression-free survival in univariate analysis for patients with postchernotherapy effusions. PTEN expression was low in effusions and solid tumors (23% and 13%, respectively), and its expression showed no association with DJ-1 levels or survival. Our data show that DJ-1 is frequently expressed in advanced-stage ovarian carcinoma at all anatomical sites and is coexpressed with its transcriptional regulators Sp1 and Sp3. In contrast, PTEN expression is infrequent in this disease. These findings may provide one of the molecular mechanisms that mediate cancer cell survival and aggressiveness in this tumor. (c) 2008 Elsevier Inc. All rights reserved.