cdc25a and the splicing variant cdc25b2, but not cdc25B1, -B3 or -C, are over-expressed in aggressive human non-Hodgkin's lymphomas

Abstract

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.