Requirement for cyclin D3 in lymphocyte development and T cell leukemias

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 gen...

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Bibliographic Details
Published in:Cancer cell 2003-12, Vol.4 (6), p.451-461
Main Authors: Sicinska, Ewa, Aifantis, Iannis, Le Cam, Laurent, Swat, Wojciech, Borowski, Christine, Yu, Qunyan, Ferrando, Adolfo A, Levin, Steven D, Geng, Yan, von Boehmer, Harald, Sicinski, Piotr
Format: Article
Language:English
Subjects:
Animals
Bone Marrow - metabolism
Cell Cycle - physiology
Cell Differentiation - physiology
Cyclin D1 - metabolism
Cyclin D2
Cyclin D3
Cyclins - metabolism
Flow Cytometry
Humans
Leukemia, T-Cell - etiology
Leukemia, T-Cell - metabolism
Leukemia, T-Cell - pathology
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) - metabolism
Lymphocytes - cytology
Lymphocytes - metabolism
Membrane Proteins
Mice
Mice, Knockout
Models, Animal
Oligonucleotide Array Sequence Analysis
Receptors, Notch
RNA, Small Interfering
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - metabolism
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Summary: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.
ISSN:1535-6108
1878-3686
DOI:10.1016/S1535-6108(03)00301-5