Endogenous oncogenic K-ras(G12D) stimulates proliferation and widespread neoplastic and developmental defects.
Cancer Cell
; 5(4): 375-87, 2004 Apr.
Article
em En
| MEDLINE
| ID: mdl-15093544
ABSTRACT
Activating mutations in the ras oncogene are not considered sufficient to induce abnormal cellular proliferation in the absence of cooperating oncogenes. We demonstrate that the conditional expression of an endogenous K-ras(G12D) allele in murine embryonic fibroblasts causes enhanced proliferation and partial transformation in the absence of further genetic abnormalities. Interestingly, K-ras(G12D)-expressing fibroblasts demonstrate attenuation and altered regulation of canonical Ras effector signaling pathways. Widespread expression of endogenous K-ras(G12D) is not tolerated during embryonic development, and directed expression in the lung and GI tract induces preneoplastic epithelial hyperplasias. Our results suggest that endogenous oncogenic ras is sufficient to initiate transformation by stimulating proliferation, while further genetic lesions may be necessary for progression to frank malignancy.
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Base de dados:
MEDLINE
Assunto principal:
Anormalidades Congênitas
/
Transformação Celular Neoplásica
/
Genes ras
/
Regulação da Expressão Gênica no Desenvolvimento
/
Fibroblastos
/
Neoplasias
Limite:
Animals
Idioma:
En
Revista:
Cancer Cell
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2004
Tipo de documento:
Article