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
Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Cancer Cell. 2003 Dec;4(6):451-61. doi: 10.1016/s1535-6108(03)00301-5.
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.
D型细胞周期蛋白（细胞周期蛋白D1、D2和D3）是哺乳动物细胞核心细胞周期机制的组成部分。细胞周期蛋白D3基因发生重排，其蛋白在几种人类淋巴恶性肿瘤中过表达。为了确定细胞周期蛋白D3在发育和肿瘤发生中的功能，我们构建并分析了细胞周期蛋白D3缺陷型小鼠。我们发现，细胞周期蛋白D3基因敲除（-/-）的动物无法使未成熟T淋巴细胞正常扩增，并且对特定致癌途径引发的T细胞恶性肿瘤的易感性大大降低。细胞周期蛋白D3在人类恶性肿瘤中也发挥作用，因为敲低细胞周期蛋白D3可抑制源自未成熟T淋巴细胞的急性淋巴细胞白血病的增殖。这些研究表明，细胞周期蛋白D3是特定人类恶性肿瘤治疗干预的潜在靶点。
