Author/Authors :
Yu، نويسنده , , Qunyan and Sicinska، نويسنده , , Ewa and Geng، نويسنده , , Yan and Ahnstrِm، نويسنده , , Marie and Zagozdzon، نويسنده , , Agnieszka and Kong، نويسنده , , Yinxin and Gardner، نويسنده , , Humphrey and Kiyokawa، نويسنده , , Hiroaki and Harris، نويسنده , , Lyndsay N. and Stهl، نويسنده , , Olle and Sicinski، نويسنده , , Piotr، نويسنده ,
Abstract :
Summary
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.
