AKT1 Activation Promotes Development of Melanoma Metastases.
Cell Rep
; 13(5): 898-905, 2015 Nov 03.
Article
em En
| MEDLINE
| ID: mdl-26565903
ABSTRACT
Metastases are the major cause of melanoma-related mortality. Previous studies implicating aberrant AKT signaling in human melanoma metastases led us to evaluate the effect of activated AKT1 expression in non-metastatic BRAF(V600E)/Cdkn2a(Null) mouse melanomas in vivo. Expression of activated AKT1 resulted in highly metastatic melanomas with lung and brain metastases in 67% and 17% of our mice, respectively. Silencing of PTEN in BRAF(V600E)/Cdkn2a(Null) melanomas cooperated with activated AKT1, resulting in decreased tumor latency and the development of lung and brain metastases in nearly 80% of tumor-bearing mice. These data demonstrate that AKT1 activation is sufficient to elicit lung and brain metastases in this context and reveal that activation of AKT1 is distinct from PTEN silencing in metastatic melanoma progression. These findings advance our knowledge of the mechanisms driving melanoma metastasis and may provide valuable insights for clinical management of this disease.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Neoplasias Encefálicas
/
Proteínas Proto-Oncogênicas c-akt
/
Neoplasias Pulmonares
/
Melanoma
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Estados Unidos