Requirement for CDK4 kinase function in breast cancer

被引：340

作者：

Yu, QY

Sicinska, E

Geng, Y

Ahnström, M

Zagozdzon, A

Kong, YX

Gardner, H

Kiyokawa, H

Harris, LN

Stål, O

Sicinski, P ^{[1
]}

机构：

[1] Harvard Univ, Sch Med, Dept Canc Biol, Dana Farber Canc Inst, Boston, MA 02215 USA

[2] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02215 USA

[3] Linkoping Univ, Fac Hlth Sci, Div Oncol, Dept Biomed & Surg, SE-58185 Linkoping, Sweden

[4] Biogen Inc, Dept Pathol Res, Cambridge, MA 02142 USA

[5] Northwestern Univ, Dept Mol Pharmacol & Biochem Chem, Chicago, IL 60611 USA

[6] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[7] Brigham & Womens Hosp, Boston, MA 02215 USA

来源：

CANCER CELL | 2006年 / 9卷 / 01期

关键词：

D O I：

10.1016/j.ccr.2005.12.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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

引用

页码：23 / 32

页数：10

共 59 条

[1] Cyclin D1 associates with the TBP-associated factor TAFII250 to regulate Sp1-mediated transcription [J].