title: Requirement for cyclin D3 in lymphocyte development and T cell leukemias.
abstract: The D-type cyclins (cyclins D1, D2, and D3) are components of the core cell cycle machinery in mammalian cells. Cyclin D3 gene is rearranged and the protein is overexpressed in several human lymphoid malignancies. In order to determine the function of cyclin D3 in development and oncogenesis, we generated and analyzed cyclin D3-deficient mice. We found that cyclin D3(-/-) animals fail to undergo normal expansion of immature T lymphocytes and show greatly reduced susceptibility to T cell malignancies triggered by specific oncogenic pathways. The requirement for cyclin D3 also operates in human malignancies, as knock-down of cyclin D3 inhibited proliferation of acute lymphoblastic leukemias deriving from immature T lymphocytes. These studies point to cyclin D3 as a potential target for therapeutic intervention in specific human malignancies.
authors.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sicinska
authors.forename: Iannis
authors.initials: I
authors.lastname: Aifantis
authors.forename: Laurent
authors.initials: L
authors.lastname: Le Cam
authors.forename: Wojciech
authors.initials: W
authors.lastname: Swat
authors.forename: Christine
authors.initials: C
authors.lastname: Borowski
authors.forename: Qunyan
authors.initials: Q
authors.lastname: Yu
authors.forename: Adolfo A
authors.initials: AA
authors.lastname: Ferrando
authors.forename: Steven D
authors.initials: SD
authors.lastname: Levin
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Harald
authors.initials: H
authors.lastname: von Boehmer
authors.forename: Piotr
authors.initials: P
authors.lastname: Sicinski
mesh_terms: D000818:Animals; D001853:Bone Marrow / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D019938:Cyclin D1 / Q000378:metabolism; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D015458:Leukemia, T-Cell / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C080336:CCND2 protein, human; C534696:CCND3 protein, human; C486196:Ccnd2 protein, mouse; C534697:Ccnd3 protein, mouse; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D051880:Receptors, Notch; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)