English   español  
Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/24317
Compartir / Impacto:
Add this article to your Mendeley library MendeleyBASE
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL

The MDM2 oncoprotein promotes apoptosis in p53-deficient human medullary thyroid carcinoma cells

AutorDilla, Tatiana; Velasco, Juan A.; Medina, Diego L.; González-Palacios, J. Fernando; Santisteban, Pilar
Fecha de publicaciónene-2000
EditorEndocrine Society
CitaciónEndocrinology 141(1): 420-429 (2000)
ResumenThe MDM2 oncoprotein has been shown to inhibit p53-mediated growth arrest and apoptosis. It also confers growth advantage to different cell lines in the absence of p53. Recently, the ability of MDM2 to arrest the cell cycle of normal human fibroblasts has also been described. We report a novel function for this protein, showing that overexpression of MDM2 promotes apoptosis in p53-deficient, human medullary thyroid carcinoma cells. These cells, devoid of endogenous MDM2 protein, exhibited a significant growth retardation after stable transfection with mdm2. Cell cycle distribution of MDM2 transfectants [medullary thyroid tumor (MTT)-mdm2] revealed a fraction of the cell population in a hypodiploid status, suggesting that MDM2 is sufficient to promote apoptosis. This circumstance is further demonstrated by annexin V labeling. MDM2-induced apoptosis is partially reverted by transient transfection with p53 and p19ARF. Both MTT and MTT-mdm2 cells were tumorigenic when injected into nude mice. However, the percentage ofapoptotic nuclei in tumor sections derived from MDM2-expressing cells was significantly higher relative to that in the parental cell line. MDM2-mediated programmed cell death is at least mediated by a down-regulation of the antiapoptotic protein Bcl-2. Protein levels of caspase-2, which are undetectable in the parental cell line, appear clearly elevated in MTT-mdm2 cells. Caspase-3 activation does not participate in MDM2-induced apoptosis, as determined by protein levels or poly(ADP-ribose) polymerase fragmentation. The results observed in this medullary carcinoma cell line show for the first time that the product of the mdm2 oncogene mediates cell death by apoptosis in p53-deficient tumor cells.
Descripción10 pages, 7 figures, 4 tables.
Versión del editorhttp://dx.doi.org/10.1210/en.141.1.420
Aparece en las colecciones: (IIBM) Artículos
Ficheros en este ítem:
Fichero Descripción Tamaño Formato  
The MDM2.pdf3,13 MBAdobe PDFVista previa
Mostrar el registro completo

Artículos relacionados:

NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.