Cyclin-dependent kinase 4 expression is essential for neu-induced breast tumorigenesis.
Cancer Res
; 65(22): 10174-8, 2005 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-16288002
ABSTRACT
Previous work has shown that cyclin D1 expression is required for neu- and ras-induced, but not wnt- or c-myc-induced, breast tumorigenesis in mice. Although cyclin D1 binds and activates cyclin-dependent kinase 4 (Cdk4), thereby mediating activation of a program of E2F-dependent gene expression, it has been suggested that the oncogenic activities of cyclin D1 are independent of Cdk4. To determine whether Cdk4 expression is required for breast tumorigenesis in mice, we have generated compound mice ectopically expressing the neu or wnt oncogenes in the mammary glands of wild-type and Cdk4-/- mice. Our results show that Cdk4 expression is required for efficient neu-induced tumorigenesis but is dispensable for wnt-induced breast tumorigenesis. In contrast to results previously observed in the mammary glands of cyclin D1-/- virgin females, our results show defects in mammary gland development in Cdk4-/- virgin females, suggesting differences in compensatory mechanisms in the absence of either subunit of the cyclin D1/Cdk4 complex. These results suggest that drugs targeted to inhibit Cdk4 activities could be developed to specifically treat certain breast tumors as Cdk4 is not essential for viability.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Transformación Celular Neoplásica
/
Genes erbB-2
/
Quinasa 4 Dependiente de la Ciclina
/
Neoplasias Mamarias Experimentales
Límite:
Animals
Idioma:
En
Revista:
Cancer Res
Año:
2005
Tipo del documento:
Article
País de afiliación:
Estados Unidos