Hernández S, Hernández L, Bea S, Pinyol M, Nayach I, Bellosillo B, Nadal A, Ferrer A, Fernández P L, Montserrat E, Cardesa A, Campo E
Department of Pathology, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain.
Int J Cancer. 2000 Mar 20;89(2):148-52.
cdc25 is a family of phosphatases that activate the cyclin-dependent kinases at different points of the cell cycle. cdc25A and -B, but not -C, have been shown to have oncogenic potential. Three different splicing variants of the cdc25B gene, cdc25B1, -B2 and -B3, have also been identified. Experimental studies suggest that cdc25B2 may be more active in vivo than cdc25B3 and -B1, but the relative expression of these splicing variants in human tumors is not known. In this study, we have analyzed the expression of cdc25A, -B1, -B2, -B3 and -C mRNA in 9 non-neoplastic lymphoid samples, 89 non-Hodgki&ngrave;s lymphomas and 9 hematological cancer cell lines by semi-quantitative RT-PCR. cdc25A, -B and -C protein expression was examined by Western blot. Normal peripheral blood lymphocytes and reactive tissues expressed cdc25B1 and -B3 mRNA and very low or undetectable levels of cdc25A, -B2 and -C. High levels of cdc25A and cdc25B2 were found in 35% and 39% of the tumors, respectively, and they were more frequently observed in aggressive than in indolent lymphomas. cdc25B1 and -B3 splice variants were detected in virtually all tumors, and no significant differences were found between high- and low-grade lymphomas. cdc25A and -B protein expression was also higher in aggressive than in indolent lymphomas. cdc25C expression was relatively low in virtually all cases. In conclusion, these findings suggest that cdc25A and -B2, but not cdc25B1, -B3 and -C, are over-expressed in a relatively large number of malignant lymphomas and may participate in the pathogenesis of aggressive variants.
细胞周期蛋白依赖性激酶25（cdc25）是一类磷酸酶家族，可在细胞周期的不同时间点激活细胞周期蛋白依赖性激酶。已证实cdc25A和 -B具有致癌潜力，而cdc25C则没有。cdc25B基因还有三种不同的剪接变体，即cdc25B1、-B2和 -B3。实验研究表明，cdc25B2在体内可能比cdc25B3和 -B1更具活性，但这些剪接变体在人类肿瘤中的相对表达情况尚不清楚。在本研究中，我们通过半定量逆转录聚合酶链反应（RT-PCR）分析了9份非肿瘤性淋巴样样本、89例非霍奇金淋巴瘤和9种血液系统癌细胞系中cdc25A、-B1、-B2、-B3和 -C mRNA的表达情况。通过蛋白质印迹法检测了cdc25A、-B和 -C蛋白的表达。正常外周血淋巴细胞和反应性组织表达cdc25B1和 -B3 mRNA，而cdc25A、-B2和 -C的表达水平极低或无法检测到。分别在35%和39%的肿瘤中发现高水平的cdc25A和cdc25B2，并且在侵袭性淋巴瘤中比在惰性淋巴瘤中更常见。几乎在所有肿瘤中都检测到了cdc25B1和 -B3剪接变体，并在高级别和低级别淋巴瘤之间未发现显著差异。侵袭性淋巴瘤中cdc25A和 -B蛋白的表达也高于惰性淋巴瘤。几乎在所有病例中cdc25C的表达都相对较低。总之，这些发现表明，cdc25A和 -B2在相对大量的恶性淋巴瘤中过度表达，而cdc25B1、-B3和 -C则不然，并且可能参与侵袭性变体的发病机制。
