Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin.
Cancer Cell
; 10(2): 159-70, 2006 Aug.
Article
em En
| MEDLINE
| ID: mdl-16904613
ABSTRACT
Endothelial cells in growing tumors express activated Akt, which when modeled by transgenic endothelial expression of myrAkt1 was sufficient to recapitulate the abnormal structural and functional features of tumor blood vessels in nontumor tissues. Sustained endothelial Akt activation caused increased blood vessel size and generalized edema from chronic vascular permeability, while acute permeability in response to VEGF-A was unaffected. These changes were reversible, demonstrating an ongoing requirement for Akt signaling for the maintenance of these phenotypes. Furthermore, rapamycin inhibited endothelial Akt signaling, vascular changes from myrAkt1, tumor growth, and tumor vascular permeability. Akt signaling in the tumor vascular stroma was sensitive to rapamycin, suggesting that rapamycin may affect tumor growth in part by acting as a vascular Akt inhibitor.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Endotélio Vascular
/
Sirolimo
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Células Endoteliais
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Proteínas Proto-Oncogênicas c-akt
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Neoplasias
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Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Estados Unidos