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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Sánchez-Beato, M. Articles by Piris, M. A. Search for Related Content PubMed PubMed Citation Articles by Sánchez-Beato, M. Articles by Piris, M. A. Related Collections Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, Vol. 94 No. 2 (July 15), 1999: pp. 765-772 Anomalous High p27/KIP1 Expression in a Subset of Aggressive B-Cell Lymphomas Is Associated With Cyclin D3 Overexpression. p27/KIP1Cyclin D3 Colocalization in Tumor Cells Margarita Sánchez-Beato, Francisca I. Camacho, Juan C. Martínez-Montero, Ana I. Sáez, Raquel Villuendas, Lydia Sánchez-Verde, Juan F. García, and Miguel A. Piris From the Department of Genetics and Department of Pathology, Virgen de la Salud Hospital, Toledo, Spain. p27 cyclin-dependent kinase inhibitor downregulation is essential for transition to the S phase of the cell cycle. Thus, proliferating cells in reactive lymphoid tissue show no detectable p27 expression. Nevertheless, anomalous high p27 expression has been shown to be present in a group of aggressive B-cell lymphomas with high proliferation index and adverse clinical outcome. This suggests that abnormally accumulated p27 protein has been rendered functionally inactive. We analyzed the causes of this anomalous presence of p27 in a group of aggressive B-cell lymphomas, including 54 cases of diffuse large B-cell lymphomas and 20 Burkitt's lymphomas. We simultaneously studied them for p27, cyclin D3, cyclin D2, cyclin D1, and cyclin E expression, because it has been stated that high levels of expression of cyclin D1 or E lead to increased p27 levels in some cell types. A statistically significant association between p27 and cyclin D3 expression was found for the group as a whole. Additionally, when dividing the cases according to the level of expression of cyclin D3 by reactive germinal centers, it was observed that cases with stronger cyclin D3 expression also show higher p27 expression. The relationship between both proteins was also shown at a subcellular level by laser confocal studies, showing that in cases with high expression of both proteins there was a marked colocalization. Additional evidence in favor of p27 sequestration by cyclin D3 was provided by coimmunoprecipitation studies in a Burkitt's cell line (Raji) showing the existence of cyclin D3/p27 complexes and the absence of CDK2/p27 complexes. These results could support the hypothesis that there are cyclin D3/p27 complexes in a subset of aggressive B-cell lymphomas in which p27 lacks the inhibitory activity found when it is bound to cyclin E/CDK2 complexes. This interaction between both proteins could lead to an abnormal nuclear accumulation, detectable by immunohistochemical techniques. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Besson, H. C. Hwang, S. Cicero, S. L. Donovan, M. Gurian-West, D. Johnson, B. E. Clurman, M. A. Dyer, and J. M. Roberts Discovery of an oncogenic activity in p27Kip1 that causes stem cell expansion and a multiple tumor phenotype Genes & Dev., July 15, 2007; 21(14): 1731 - 1746. 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