beta-Catenin regulates vascular endothelial growth factor expression in colon cancer.
Cancer Res
; 63(12): 3145-53, 2003 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-12810642
ABSTRACT
To evaluate whether beta-catenin signaling has a role in the regulation of angiogenesis in colon cancer, a series of angiogenesis-related gene promoters was analyzed for beta-catenin/TCF binding sites. Strikingly, the gene promoter of human vascular endothelial growth factor (VEGF, or VEGF-A) contains seven consensus binding sites for beta-catenin/TCF. Analysis of laser capture microdissected human colon cancer tissue indicated a direct correlation between up-regulation of VEGF-A expression and adenomatous polyposis coli (APC) mutational status (activation of beta-catenin signaling) in primary tumors. In metastases, this correlation was not observed. Analysis by immunohistochemistry of intestinal polyps in mice heterozygous for the multiple intestinal neoplasia gene (Min/+) at 5 months revealed an increase and redistribution of VEGF-A in proximity to those cells expressing nuclear beta-catenin with a corresponding increase in vessel density. Transfection of normal colon epithelial cells with activated beta-catenin up-regulated levels of VEGF-A mRNA and protein by 250-300%. When colon cancer cells with elevated beta-catenin levels were treated with beta-catenin antisense oligodeoxynucleotides, VEGF-A expression was reduced by more than 50%. Taken together, our observations indicate a close link between beta-catenin signaling and the regulation of VEGF-A expression in colon cancer.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenocarcinoma
/
Regulación Neoplásica de la Expresión Génica
/
Transactivadores
/
Factores de Crecimiento Endotelial
/
Linfocinas
/
Regiones Promotoras Genéticas
/
Neoplasias del Colon
/
Proteínas del Citoesqueleto
/
Péptidos y Proteínas de Señalización Intercelular
/
Proteínas de Neoplasias
Tipo de estudio:
Etiology_studies
Idioma:
En
Revista:
Cancer Res
Año:
2003
Tipo del documento:
Article
País de afiliación:
Estados Unidos