Author/Authors :
Sicinska، نويسنده , , Ewa and Aifantis، نويسنده , , Iannis and Le Cam، نويسنده , , Laurent and Swat، نويسنده , , Wojciech and Borowski، نويسنده , , Christine and Yu، نويسنده , , Qunyan and Ferrando، نويسنده , , Adolfo A and Levin، نويسنده , , Steven D and Geng، نويسنده , , Yan and von Boehmer، نويسنده , , Harald and Sicinski، نويسنده , , Piotr، نويسنده ,
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.
