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 ; 64(17): 6127-36, 2004 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-15342396

RESUMEN

Sprouty (Spry) proteins were found to be endogenous inhibitors of the Ras/mitogen-activated protein kinase pathway that play an important role in the remodeling of branching tissues. We investigated Spry expression levels in various cancers and found that Spry1 and Spry2 were down-regulated consistently in breast cancers. Such prevalent patterns of down-regulation may herald the later application of these isoforms as tumor markers that are breast cancer specific and more profound than currently characterized markers. Spry1 and 2 were expressed specifically in the luminal epithelial cells of breast ducts, with higher expression during stages of tissue remodeling when the epithelial ducts are forming and branching. These findings suggest that Sprys might be involved as a modeling counterbalance and surveillance against inappropriate epithelial expansion. The abrogation of endogenous Spry activity in MCF-7 cells by the overexpression of a previously characterized dominant-negative mutant of Spry, hSpry2Y55F resulted in enhanced cell proliferation in vitro. The hSpry2Y55F stably expressing cells also formed larger and greater number of colonies in the soft-agar assay. An in vivo nude mice assay showed a dramatic increase in the tumorigenic potential of hSpry2Y55F stable cells. The consistent down-regulation of Spry1 and 2 in breast cancer and the experimental evidence using a dominant-negative hSpry2Y55F indicate that Spry proteins may actively maintain tissue integrity that runs amok when their expression is decreased below normal threshold levels. This alludes to a previously unrecognized role for Sprys in cancer development.


Asunto(s)
Neoplasias de la Mama/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Proteínas de la Membrana/biosíntesis , Fosfoproteínas/biosíntesis , Biosíntesis de Proteínas , Proteínas Adaptadoras Transductoras de Señales , Animales , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , División Celular/fisiología , Línea Celular Tumoral , Regulación hacia Abajo , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Silenciador del Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular , Glándulas Mamarias Animales/metabolismo , Glándulas Mamarias Animales/fisiología , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Ratones , Ratones Endogámicos BALB C , Fosfoproteínas/antagonistas & inhibidores , Fosfoproteínas/genética , Proteínas Serina-Treonina Quinasas , Proteínas/antagonistas & inhibidores , Proteínas/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transfección , Trasplante Heterólogo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA