The p110α and p110ß isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis.
Genes Dev
; 26(14): 1573-86, 2012 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-22802530
ABSTRACT
Class Ia phosphatidylinositol 3 kinase (PI3K) is required for oncogenic receptor-mediated transformation; however, the individual roles of the two commonly expressed class Ia PI3K isoforms in oncogenic receptor signaling have not been elucidated in vivo. Here, we show that genetic ablation of p110α blocks tumor formation in both polyoma middle T antigen (MT) and HER2/Neu transgenic models of breast cancer. Surprisingly, p110ß ablation results in both increased ductal branching and tumorigenesis. Biochemical analyses suggest a competition model in which the less active p110ß competes with the more active p110α for receptor binding sites, thereby modulating the level of PI3K activity associated with activated receptors. Our findings demonstrate a novel p110ß-based regulatory role in receptor-mediated PI3K activity and identify p110α as an important target for treatment of HER2-positive disease.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Mamárias Animais
/
Transformação Celular Neoplásica
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Classe I de Fosfatidilinositol 3-Quinases
/
Glândulas Mamárias Animais
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Genes Dev
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos