Requirement for CDK4 kinase function in breast cancer.

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 (approximately 25%) of ErbB-2-overexpressing tumors. We propose that this subset of breast cancer patients might benefit from inhibiting CDK4 kinase.

• Authors: Qunyan Yu, Ewa Sicinska, Yan Geng, Marie Ahnström, Agnieszka Zagozdzon, Yinxin Kong, Humphrey Gardner, Hiroaki Kiyokawa, Lyndsay N Harris, Olle Stål, Piotr Sicinski
• Journal: Cancer cell (Cancer Cell) Vol. 9 Issue 1 Pg. 23-32 (Jan 2006) ISSN: 1535-6108 [Print] United States
• PMID: 16413469 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclin D1
• Cyclin-Dependent Kinase 4

Topics

• Animals
• Breast Neoplasms (enzymology, genetics, pathology)
• Cell Proliferation
• Cyclin D1 (genetics, metabolism)
• Cyclin-Dependent Kinase 4 (genetics, metabolism)
• Enzyme Activation
• Female
• Genes, erbB-2
• Humans
• Mammary Neoplasms, Experimental (enzymology, pathology)
• Mice
• Mice, Knockout
• Protein Binding