Journal
CANCER CELL
Volume 9, Issue 1, Pages 13-22Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2005.12.019
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Funding
- NATIONAL CANCER INSTITUTE [R01CA083688, R01CA096527] Funding Source: NIH RePORTER
- NCI NIH HHS [CA096527, CA083688] Funding Source: Medline
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Cyclin D1 is a multifunctional protein that activates CDK4 and CDK6, titrates Cip/Kip CDK inhibitors to increase CDK2 activity, and modulates the function of certain transcription factors. To specifically test the importance of cyclin D1-associated kinase activity, we generated knockin mice expressing mutant cyclin D1 deficient in activating CDK4/6. The development of several cyclin D1-dependent compartments, including mammary glands, proceeds relatively normally in these animals, demonstrating that cyclin D1-associated kinase activity is largely dispensable for development of these tissues. Strikingly, knockin mice were resistant to breast cancers initiated by ErbB-2. These results demonstrate a differential requirement for cyclin D1-CDK4/6 kinase activity in development versus tumorigenesis and strongly support cyclin D1-dependent kinase activity as a specific therapeutic target in breast cancer.
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