title: Cyclin D1 expression in mantle cell lymphoma is accompanied by downregulation of cyclin D3 and is not related to the proliferative activity.
abstract: The cell cycle regulatory protein cyclin D1 is essential for G1-S phase transition in several epithelial and mesenchymal tissues but is apparently not essential in normal mature B cells. An overexpression of cyclin D1 is induced by the chromosomal translocation t(11;14)(q13;q32), which characterizes non-Hodgkin's lymphomas (NHLs) of mantle cell type. We studied 26 cases of mantle cell lymphoma (MCL) for the expression of cyclins D1 and D3. A total of 23 lymphomas showed a nuclear staining for cyclin D1, whereas reactive B cells of residual germinal centers were constantly negative. When compared with cyclin D3, an inverse staining pattern emerged. Whereas the B cells of residual germinal centers reacted strongly positive for cyclin D3, there was low or missing expression of cyclin D3 in MCL cells. In other B-cell lymphomas (n = 55), including chronic lymphocytic leukemia, low-grade lymphomas of mucosa-associated lymphatic tissue, follicular lymphomas, and diffuse large B-cell lymphomas, no cyclin D1 expression could be detected and 89% of these cases displayed cyclin D3 positivity. Lymphoma cell lines harboring the t(11;14) showed cyclin D1 protein but no or very low levels of cyclin D3; three other B-cell lines, a T-cell line, and peripheral blood lymphocytes strongly expressed cyclin D3 and reacted negatively for cyclin D1. We conclude that the chromosomal translocation t(11;14) leads to an abnormal protein expression of cyclin D1 in the tumor cells of MCL and induces a consecutive downregulation of cyclin D3. In contrast to other B-NHLs, cyclin D1 and D3 expression in MCL is not related to the growth fraction.
authors.affiliation: Institute of Pathology, University of Würzburg, Germany.
authors.forename: M M
authors.initials: MM
authors.lastname: Ott
authors.forename: J
authors.initials: J
authors.lastname: Bartkova
authors.forename: J
authors.initials: J
authors.lastname: Bartek
authors.forename: A
authors.initials: A
authors.lastname: Dürr
authors.forename: L
authors.initials: L
authors.lastname: Fischer
authors.forename: G
authors.initials: G
authors.lastname: Ott
authors.forename: H K
authors.initials: HK
authors.lastname: Müller-Hermelink
authors.forename: H
authors.initials: H
authors.lastname: Kreipe
mesh_terms: D002455:Cell Division; D019938:Cyclin D1 / Q000096:biosynthesis*; D056743:Cyclin D3; D016213:Cyclins / Q000096:biosynthesis*; D015536:Down-Regulation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics / Q000473:pathology; D018442:Lymphoma, B-Cell, Marginal Zone / Q000235:genetics / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics* / Q000473:pathology; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C534696:CCND3 protein, human; D056743:Cyclin D3; D016213:Cyclins; D019938:Cyclin D1