The requirement for cyclin D function in tumor maintenance

Cancer Cell. 2012 Oct 16;22(4):438-51. doi: 10.1016/j.ccr.2012.09.015.


D-cyclins 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Cycle Checkpoints
  • Cyclin D / antagonists & inhibitors
  • Cyclin D / physiology*
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Female
  • Humans
  • Mammary Neoplasms, Experimental / etiology
  • Mice
  • Neoplasms / drug therapy
  • Neoplasms / etiology*
  • Neoplasms / pathology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / drug therapy
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / etiology
  • Receptor, ErbB-2 / analysis


  • Cyclin D
  • Erbb2 protein, mouse
  • Receptor, ErbB-2
  • Cyclin-Dependent Kinase 4

Associated data

  • GEO/GSE40514