title: 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.affiliation: Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: Qunyan
authors.initials: Q
authors.lastname: Yu
authors.forename: Ewa
authors.initials: E
authors.lastname: Sicinska
authors.forename: Yan
authors.initials: Y
authors.lastname: Geng
authors.forename: Marie
authors.initials: M
authors.lastname: Ahnström
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zagozdzon
authors.forename: Yinxin
authors.initials: Y
authors.lastname: Kong
authors.forename: Humphrey
authors.initials: H
authors.lastname: Gardner
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kiyokawa
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: Olle
authors.initials: O
authors.lastname: Stål
authors.forename: Piotr
authors.initials: P
authors.lastname: Sicinski
mesh_terms: 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
chemical_list: D019938:Cyclin D1; D051358:Cyclin-Dependent Kinase 4