Author/Authors :
Choi، نويسنده , , Yoon Jong and Li، نويسنده , , Xiaoyu and Hydbring، نويسنده , , Per and Sanda، نويسنده , , Takaomi and Stefano، نويسنده , , Joanna and Christie، نويسنده , , Amanda L. and Signoretti، نويسنده , , Sabina and Look، نويسنده , , A. Thomas and Kung، نويسنده , , Andrew L. and von Boehmer، نويسنده , , Harald and Sicinski، نويسنده , , Piotr، نويسنده ,
Abstract :
Summary
ins represent components of cell cycle machinery. To test the efficacy of targeting D-cyclins in cancer treatment, we engineered mouse strains that allow acute and global ablation of individual D-cyclins in a living animal. Ubiquitous shutdown of cyclin D1 or inhibition of cyclin D-associated kinase activity in mice bearing ErbB2-driven mammary carcinomas triggered tumor cell senescence, without compromising the animals’ health. Ablation of cyclin D3 in mice bearing Notch1-driven T cell acute lymphoblastic leukemias (T-ALL) triggered tumor cell apoptosis. Such selective killing of leukemic cells can also be achieved by inhibiting cyclin D associated kinase activity in mouse and human T-ALL models. Inhibition of cyclin D-kinase activity represents a highly-selective anticancer strategy that specifically targets cancer cells without significantly affecting normal tissues.
