Requirement for CDK4 Kinase Function in Breast Cancer

Cancer Cell. 2006 Jan;9(1):23-32. doi: 10.1016/j.ccr.2005.12.012.

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.

Publication types

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

MeSH terms

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

Substances

  • Cyclin D1
  • Cyclin-Dependent Kinase 4