title: Cyclin D2 is overexpressed in proliferation centers of chronic lymphocytic leukemia/small lymphocytic lymphoma.
abstract: The D cyclins are important cell cycle regulatory proteins involved in the pathogenesis of some lymphomas. Cyclin D1 overexpression is a hallmark of mantle cell lymphoma, whereas cyclins D2 and D3 have not been shown to be closely associated with any particular subtype of lymphoma. In the present study, we found that cyclin D2 was specifically overexpressed in the proliferation centers (PC) of all cases of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) examined (19/19). To examine the molecular mechanisms underlying this overexpression, we immunohistochemically examined the expression of nuclear factor (NF)-κB, p15, p16, p18, and p27 in the PC of six patients. Five cases showed upregulation of NF-κB expression, which is known to directly induce cyclin D2 by binding to the promoter region of CCND2. All six PC examined demonstrated downregulation of p27 expression. In contrast, upregulation of p15 expression was detected in five of six PC examined. This discrepancy suggests that unknown cell cycle regulatory mechanisms involving NF-κB-related pathways are also involved, because NF-κB upregulates cyclin D2 not only directly, but also indirectly through c-Myc, which is believed to downregulate both p27 and p15. In conclusion, cyclin D2 is overexpressed in the PC of CLL/SLL and this overexpression is due, in part, to the upregulation of NF-κB-related pathways.
authors.affiliation: Department of Pathology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Igawa
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sato
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Takata
authors.forename: Soichiro
authors.initials: S
authors.lastname: Fushimi
authors.forename: Maiko
authors.initials: M
authors.lastname: Tamura
authors.forename: Naoya
authors.initials: N
authors.lastname: Nakamura
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
authors.forename: Yorihisa
authors.initials: Y
authors.lastname: Orita
authors.forename: Mitsune
authors.initials: M
authors.lastname: Tanimoto
authors.forename: Tadashi
authors.initials: T
authors.lastname: Yoshino
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056742:Cyclin D2 / Q000096:biosynthesis* / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000378:metabolism* / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014066:Palatine Tonsil / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation; D051746:ZAP-70 Protein-Tyrosine Kinase / Q000096:biosynthesis / Q000235:genetics
chemical_list: C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D051746:ZAP-70 Protein-Tyrosine Kinase; C497261:ZAP70 protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1