Somatic mutations in p85alpha promote tumorigenesis through class IA PI3K activation.
Cancer Cell
; 16(6): 463-74, 2009 Dec 08.
Article
em En
| MEDLINE
| ID: mdl-19962665
ABSTRACT
Members of the mammalian phosphoinositide-3-OH kinase (PI3K) family of proteins are critical regulators of various cellular process including cell survival, growth, proliferation, and motility. Oncogenic activating mutations in the p110alpha catalytic subunit of the heterodimeric p110/p85 PI3K enzyme are frequent in human cancers. Here we show the presence of frequent mutations in p85alpha in colon cancer, a majority of which occurs in the inter-Src homology-2 (iSH2) domain. These mutations uncouple and retain p85alpha's p110-stabilizing activity, while abrogating its p110-inhibitory activity. The p85alpha mutants promote cell survival, AKT activation, anchorage-independent cell growth, and oncogenesis in a p110-dependent manner.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo
/
Fosfatidilinositol 3-Quinases
/
Mutação
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos