Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
Cancer Res ; 66(4): 2048-58, 2006 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-16489004

RESUMEN

The Sprouty proteins are increasingly being recognized to be deregulated in various types of cancers. This deregulation is often associated with aberrant signaling of receptor tyrosine kinases and its downstream effectors, leading to the mitogen-activated protein kinase (MAPK) signaling pathway. In human hepatocellular carcinoma, where the MAPK activity is enhanced via multiple hepatocarcinogenic factors, we observed a consistent reduced expression of the sprouty 2 (Spry2) transcript and protein in malignant hepatocytes compared with normal or cirrhotic hepatocytes. The expression pattern of Spry2 in hepatocellular carcinoma resembles that of several potential tumor markers of hepatocellular carcinoma and also that of several angiogenic factors and growth factor receptors. In contrast to previous studies of Spry2 down-regulation in other cancers, we have ruled out loss of heterozygosity or the methylation of promoter sites, two common mechanisms responsible for the silencing of genes with tumor suppressor properties. Functionally, we show that Spry2 inhibits both extracellular signal-regulated kinase signaling as well as proliferation in hepatocellular carcinoma cell lines, whereas knocking down Spry2 levels in NIH3T3 cells causes mild transformation. Our study clearly indicates a role for Spry2 in hepatocellular carcinoma, and an understanding of the regulatory controls of its expression could provide new means of regulating the angiogenic switch in this hypervascular tumor, thereby potentially controlling tumor growth.


Asunto(s)
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Proteínas/fisiología , Proteínas Adaptadoras Transductoras de Señales , Animales , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/metabolismo , Metilación de ADN , Regulación hacia Abajo , Factores de Crecimiento de Fibroblastos/farmacología , Perfilación de la Expresión Génica , Genes Supresores de Tumor , Factor de Crecimiento de Hepatocito/farmacología , Humanos , Péptidos y Proteínas de Señalización Intracelular , Cirrosis Hepática/genética , Cirrosis Hepática/metabolismo , Neoplasias Hepáticas/genética , Pérdida de Heterocigocidad , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas de la Membrana , Ratones , Células 3T3 NIH , Regiones Promotoras Genéticas , Proteínas Serina-Treonina Quinasas , Proteínas/genética , Proteínas/metabolismo , ARN Mensajero/biosíntesis , ARN Mensajero/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA