RESUMEN

The farnesoid X receptor (FXR) is a bile acid-activated nuclear receptor which is abundant in the liver, intestine, and kidney. FXR is a pivotal factor in cholesterol/bile acid homeostasis but is involved in the growth of hepatocellular carcinoma cells. In the present study, we investigated whether FXR is also involved in the growth of renal adenocarcinoma cells. The cell growth of renal adenocarcinoma cell line ACHN was inhibited by FXR knockdown and stimulated by FXR ligand, while that of a normal renal cell-derived cell line, HK-2, was not affected. The carcinoma-specific stimulation of cell growth by FXR was found to arise from down-regulation of p53 and p21/Cip1 mRNA expression. Our study showed that FXR stimulates proliferation of renal adenocarcinoma cells and that FXR knockdown is useful for growth suppression of renal adenocarcinoma without cytotoxicity to normal renal cells.

Asunto(s)

Adenocarcinoma/patología , Procesos de Crecimiento Celular/genética , Transformación Celular Neoplásica/genética , Neoplasias Renales/patología , Receptores Citoplasmáticos y Nucleares/fisiología , Adulto , Línea Celular , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Regulación hacia Abajo , Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Ligandos , Masculino , Persona de Mediana Edad , Proteína p53 Supresora de Tumor/genética , Adulto Joven