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 Detalle_Publicacion

High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression, confer resistance to apoptosis and antagonize Myc effects on cell cycle

Abstract: Myc (c-Myc) counteracts p27 effects, and low p27 usually correlates with high Myc expression in human cancer. However there is no information on the co-expression of both genes in chronic lymphocytic leukemia (CLL). We found a lack of correlation between RNA and protein levels of p27 and Myc in CLL cells, so we determined the protein levels by immunoblot in 107 cases of CLL. We observed a high p27 protein expression in CLL compared to normal B cells. Ectopic p27 expression in a CLL-derived cell line resulted in cell death resistance. Surprisingly, Myc expression was very low or undetectable in most CLL cases analyzed, with a clear correlation between high p27 and low Myc protein levels. This was associated with low Skp2 expression, which is consistent with the Skp2 role in p27 degradation and with SKP2 being a Myc target gene. High Myc expression did not correlate with leukemia progression, despite that cell cycle-related Myc target genes were upregulated. However, biochemical analysis showed that the high p27 levels inhibited cyclin-Cdk complexes even in Myc expressing CLL cells. Our data suggest that the combination of high p27 and low Myc is a marker of CLL cells which is mediated by Skp2.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Oncotarget. 2014 Jul 15;5(13):4694-708

Editorial: Impact Journals

 Fecha de publicación: 15/07/2014

Nº de páginas: 23

Tipo de publicación: Artículo de Revista

 DOI: 10.18632/oncotarget.2100

ISSN: 1949-2553

Autores/as

JUAN MANUEL CARABALLO OTERO

JUAN CARLOS ACOSTA COBACHO

MIGUEL ANGEL CORTES VAZQUEZ

MARTA ALBAJAR MOLERA

MARIA TERESA GOMEZ CASARES

MARIA ANA BATLLE LOPEZ

MARIA ANGELES CUADRADO DEL BARRIO

ARANTZA ONAINDIA PEREZ

GABRIEL BRETONES SANCHEZ

MIGUEL ANGEL PIRIS PINILLA

DOLORES COLOMER PUJOL