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

• Published in: International journal of cancer 2000-03, Vol.89 (2), p.148-152
• Main Authors: Hernández, Silvia, Hernández, Luis, Bea, Sílvia, Pinyol, Magda, Nayach, Iracema, Bellosillo, Beatriz, Nadal, Alfons, Ferrer, Ana, Fernández, Pedro L., Montserrat, Emili, Cardesa, Antonio, Campo, Elías
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Blotting, Western; cdc25 Phosphatases - analysis; cdc25 Phosphatases - genetics; cdc25A gene; cdc25B2 gene; Cell Cycle Proteins - analysis; Cell Cycle Proteins - genetics; cyclin-dependent kinase; Gene Expression Regulation, Neoplastic; Hematologic and hematopoietic diseases; Humans; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma, Non-Hodgkin - chemistry; Lymphoma, Non-Hodgkin - pathology; Medical sciences; phosphatase; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - analysis; RNA, Neoplasm - analysis; Tumor Cells, Cultured; Up-Regulation
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/(SICI)1097-0215(20000320)89:2<148::AID-IJC8>3.0.CO;2-R

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‐Hodgkin`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. Int. J. Cancer (Pred. Oncol.) 89:148–152, 2000. © 2000 Wiley‐Liss, Inc.