Suppression of Neu-induced mammary tumor growth in cyclin D1 deficient mice is compensated for by cyclin E.
Oncogene
; 21(2): 291-8, 2002 Jan 10.
Article
em En
| MEDLINE
| ID: mdl-11803472
ABSTRACT
Amplification and/or overexpression of the receptor tyrosine kinase HER2/Neu and the cell cycle regulatory gene cyclin D1 are frequently associated with human breast cancer. We studied the functional significance of cyclin D1 in Neu-induced mammary oncogenesis by developing mice overexpressing either wild-type or mutant Neu in a cyclin D1 deficient background. The absence of cyclin D1 suppresses mammary tumor formation induced by the wild-type or activated mutant form of Neu, which promote multi- and single-step progression of tumorigenesis, respectively. These data indicate that cyclin D1 is preferentially required for Neu-mediated signal transduction pathways in mammary oncogenesis. Significantly, 35% of mutant Neu/cyclin D1(-/-) mice regained mammary tumor potential due to compensation by cyclin E. Thus, shared targets of cyclins D1 and E are important in modulating Neu function in mammary tumorigenesis. Our results imply that the combinatorial inhibition of cyclins D1 and E might be useful in the treatment of malignancies induced by Neu.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Supressão Genética
/
Receptor ErbB-2
/
Genes erbB-2
/
Ciclina D1
/
Ciclina E
/
Neoplasias Mamárias Experimentais
Limite:
Animals
Idioma:
En
Revista:
Oncogene
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos