Abstract
Cyclin D1 is overexpressed in the majority of human breast cancers. We previously found that mice lacking cyclin D1 are resistant to mammary carcinomas triggered by the ErbB-2 oncogene. In this study, we investigated which function of cyclin D1 is required for ErbB-2-driven mammary oncogenesis. We report that the ability of cyclin D1 to activate cyclin-dependent kinase CDK4 underlies the critical role for cyclin D1 in breast cancer formation. We also found that the continued presence of CDK4-associated kinase activity is required to maintain breast tumorigenesis. We analyzed primary human breast cancers and found high cyclin D1 levels in a subset (∼25%) of ErbB-2-overexpressing tumors. We propose that this subset of breast cancer patients might benefit from inhibiting CDK4 kinase.
Original language | English (US) |
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Pages (from-to) | 23-32 |
Number of pages | 10 |
Journal | Cancer cell |
Volume | 9 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2006 |
Funding
The authors thank P. Hinds, M. Landis, W. Hahn, R. Possemato, R. Bronson, L. Zhang, C. Kuperwasser, and members of the Sicinski lab for help, advice, and reagents. This work was supported by an NCI R01 grant CA083688, and by a Susan G. Komen Breast Cancer Foundation grant (BCTR02-2109) to P.S.
ASJC Scopus subject areas
- Oncology
- Cancer Research