Point mutations and overexpression of Ron induce transformation, tumor formation, and metastasis.
Oncogene
; 20(43): 6142-51, 2001 Sep 27.
Article
em En
| MEDLINE
| ID: mdl-11593422
ABSTRACT
The receptor tyrosine kinase Ron is a member of the receptor family that includes the proto-oncogene Met and the avian oncogene Sea. The interaction of Ron with its ligand, known as hepatocyte growth factor-like protein (HGFL) or macrophage stimulating protein (MSP), induces crucial cellular responses including invasive growth, proliferation, cell scattering, and branching morphogenesis. Based on the homology and functional similarities between Met and Ron it was hypothesized that Ron may be important in tumor formation and metastasis. To test this hypothesis, wild-type mouse Ron and three mutant forms of Ron containing mutations similar to those found in the Met gene in human hereditary papillary renal carcinoma (HPRC), were expressed in NIH3T3 cells. A transformed phenotype was produced in cell lines expressing either wild-type Ron or the mutated Ron proteins. Further, these cell lines displayed oncogenic potential by exhibiting increased proliferation and constitutive phosphorylation of Ron. These cell lines were also tested for the ability to form solid tumors. Cells expressing wild-type Ron and the three proteins with single amino acid substitutions were highly tumorigenic in vivo. In a model of experimental metastasis, two of the cell lines with altered Ron protein formed highly aggressive tumors in the lungs. These results suggest that Ron may be an aggressive oncogene when either overexpressed or when activated by mutation.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Proto-Oncogênicas
/
Mutação Puntual
/
Fator de Crescimento de Hepatócito
/
Receptores Proteína Tirosina Quinases
/
Receptores de Superfície Celular
/
Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2001
Tipo de documento:
Article