Hernández S, Hernández L, Beà S, Cazorla M, Fernández P L, Nadal A, Muntané J, Mallofré C, Montserrat E, Cardesa A, Campo E
Department of Pathology, Institut de Investigacions Biomèdiques Agustí Pí i Sunyer, University of Barcelona, Spain.
Cancer Res. 1998 Apr 15;58(8):1762-7.
cdc25A, cdc25B, and cdc25C are a family of human phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and cdc25B have been shown to have oncogenic potential, and they have been identified as transcriptional targets of c-myc. To determine the role of cdc25 genes in the pathogenesis of human lymphomas and their possible correlation with c-myc deregulation, we have analyzed the expression of cdc25A, cdc25B, and cdc25C and c-myc genes in a series of 63 non-Hodgkin's lymphomas and 8 nonneoplastic lymphoid tissues. The mRNA levels of the three phosphatases in the nonneoplastic tissues were negative or negligible. cdc25B overexpression was detected in 35 tumors (56%). This overexpression was more frequently found in aggressive (81%) than in indolent lymphomas (36%; P < 0.01). cdc25B overexpression was also significantly associated with a higher proliferative activity of the tumors. No cdc25B gene amplification or rearrangements were detected by Southern blot analysis. A biallelic EcoRI polymorphism of cdc25B gene was identified with a similar distribution in patients with lymphoma and in a normal population. cdc25A was overexpressed in three aggressive lymphomas. No detectable cdc25C mRNA levels were seen in any of the tumors. c-myc was overexpressed in 43% of tumors, and it correlated significantly with the presence of cdc25B up-regulation. Twenty-six of 35 (74%) lymphomas with high levels of cdc25B mRNA also showed c-myc overexpression, whereas 27 of 28 (96%) tumors without detectable or with very low cdc25B expression also had undetectable c-myc levels (P < 0.0001). In addition, a significant linear correlation was found between the cdc25B and c-myc mRNA levels (r = 0.575, P < 0.001). These findings suggest that cdc25B overexpression in non-Hodkin's lymphoma may participate in the pathogenesis of aggressive variants, and it may cooperate with c-myc oncogene in the development of these tumors.
细胞周期蛋白依赖性激酶25A（cdc25A）、细胞周期蛋白依赖性激酶25B（cdc25B）和细胞周期蛋白依赖性激酶25C（cdc25C）是一类人磷酸酶，它们在细胞周期的不同阶段激活细胞周期蛋白依赖性激酶。已证明cdc25A和cdc25B具有致癌潜力，并且它们已被确定为c-myc的转录靶点。为了确定cdc25基因在人类淋巴瘤发病机制中的作用及其与c-myc失调的可能相关性，我们分析了63例非霍奇金淋巴瘤和8例非肿瘤性淋巴组织中cdc25A、cdc25B、cdc25C和c-myc基因的表达情况。非肿瘤组织中这三种磷酸酶的mRNA水平为阴性或可忽略不计。在35例肿瘤（56%）中检测到cdc25B过表达。这种过表达在侵袭性淋巴瘤（81%）中比在惰性淋巴瘤（36%；P<0.01）中更常见。cdc25B过表达也与肿瘤的较高增殖活性显著相关。Southern印迹分析未检测到cdc25B基因扩增或重排。在淋巴瘤患者和正常人群中鉴定出cdc25B基因的双等位基因EcoRI多态性，其分布相似。在3例侵袭性淋巴瘤中检测到cdc25A过表达。在任何肿瘤中均未检测到可检测到的cdc25C mRNA水平。43%的肿瘤中c-myc过表达，并且它与cdc25B上调的存在显著相关。在35例cdc25B mRNA水平高的淋巴瘤中，有26例（74%）也显示c-myc过表达，而在28例未检测到或cdc25B表达极低的肿瘤中，有27例（96%）也未检测到c-myc水平（P<0.0001）。此外，在cdc25B和c-myc mRNA水平之间发现显著的线性相关性（r = 0.575，P<0.001）。这些发现表明，非霍奇金淋巴瘤中cdc25B过表达可能参与侵袭性变体的发病机制，并且它可能在这些肿瘤的发生发展中与c-myc癌基因协同作用。
