Targeting FGF19 inhibits tumor growth in colon cancer xenograft and FGF19 transgenic hepatocellular carcinoma models.
Oncogene
; 27(1): 85-97, 2008 Jan 03.
Article
em En
| MEDLINE
| ID: mdl-17599042
ABSTRACT
Although fibroblast growth factor 19 (FGF19) can promote liver carcinogenesis in mice its involvement in human cancer is not well characterized. Here we report that FGF19 and its cognate receptor FGF receptor 4 (FGFR4) are coexpressed in primary human liver, lung and colon tumors and in a subset of human colon cancer cell lines. To test the importance of FGF19 for tumor growth, we developed an anti-FGF19 monoclonal antibody that selectively blocks the interaction of FGF19 with FGFR4. This antibody abolished FGF19-mediated activity in vitro and inhibited growth of colon tumor xenografts in vivo and effectively prevented hepatocellular carcinomas in FGF19 transgenic mice. The efficacy of the antibody in these models was linked to inhibition of FGF19-dependent activation of FGFR4, FRS2, ERK and beta-catenin. These findings suggest that the inactivation of FGF19 could be beneficial for the treatment of colon cancer, liver cancer and other malignancies involving interaction of FGF19 and FGFR4.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias do Colo
/
Carcinoma Hepatocelular
/
Marcação de Genes
/
Anticorpos Bloqueadores
/
Ensaios Antitumorais Modelo de Xenoenxerto
/
Fatores de Crescimento de Fibroblastos
/
Neoplasias Hepáticas Experimentais
/
Antineoplásicos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Oncogene
Ano de publicação:
2008
Tipo de documento:
Article