Requirement for CDK4 kinase function in breast cancer.
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.
Yu
Qunyan
Q
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Sicinska
Ewa
E
Geng
Yan
Y
Ahnström
Marie
M
Zagozdzon
Agnieszka
A
Kong
Yinxin
Y
Gardner
Humphrey
H
Kiyokawa
Hiroaki
H
Harris
Lyndsay N
LN
Stål
Olle
O
Sicinski
Piotr
P
D000818:Animals; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D005260:Female; D018734:Genes, erbB-2; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011485:Protein Binding
D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4