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

The requirement for cyclin D function in tumor maintenance.

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1
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.

Abstract

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.

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PMID:
23079655
PMCID:
PMC3487466
DOI:
10.1016/j.ccr.2012.09.015
[Indexed for MEDLINE]
Free PMC Article

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