Ras modulates Myc activity to repress thrombospondin-1 expression and increase tumor angiogenesis.
Cancer Cell
; 3(3): 219-31, 2003 Mar.
Article
em En
| MEDLINE
| ID: mdl-12676581
ABSTRACT
Tumor angiogenesis is postulated to be regulated by the balance between pro- and anti-angiogenic factors. We demonstrate that the critical step in establishing the angiogenic capability of human cells is the repression of the critical anti-angiogenic factor, thrombospondin-1 (Tsp-1). This repression is essential for tumor formation by mammary epithelial cells and kidney cells engineered to express SV40 early region proteins, hTERT, and H-RasV12. We have uncovered the signaling pathway leading from Ras to Tsp-1 repression. Ras induces the sequential activation of PI3 kinase, Rho, and ROCK, leading to activation of Myc through phosphorylation; phosphorylation of Myc via this mechanism enables it to repress Tsp-1 expression. We thus describe a novel mechanism by which the cooperative activity of the oncogenes, ras and myc, leads directly to angiogenesis and tumor formation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas ras
/
Trombospondina 1
/
Neovascularização Patológica
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos