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Título:	High p27 protein levels in chronic lymphocytic leukemia are associated to low Myc and Skp2 expression and confer resistannce to apoptosis
Autor:	León, Javier CSIC ORCID CVN
Fecha de publicación:	2014
Citación:	First Symposium Neoplasbim (2014)
Resumen:	The oncogenic transcription factor Myc (c-Myc) is usually found deregulated in human cancer. High Myc expression frequently correlates with low expression of the CDK inhibitor p27. We have recently described that MYC induces the downregulation of p27 in chronic myeloid leukemia cells through the induction of SKP2 gene, an ubiquitin ligase which targets p27 for its degradation by the proteasome. In the present work, we have analyzed Myc, Skp2 and p27 expression at RNA and/or protein levels in chronic lymphocytic leukemia (CLL) samples from two hospitals. We found no correlation between MYC and p27 RNA level and protein levels. In most samples we observed a high p27 protein expression in CLL compared to normal B cells and a low or undetectable Myc protein expression, an expression pattern which is in contrast with that observed in most human tumors. p27 was nuclear in the analyzed cases. Both proteins were studied in about 100 samples, and there was a clear correlation between high p27 and low Myc protein levels. This inverse correlation was associated with low Skp2 expression, which is consistent with the Skp2 role on p27 degradation and with SKP2 being a Myc target gene. We also found that high Myc protein expression which 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 in CLL cells were able to inhibit cyclin-Cdk complexes even in Myc overexpressing CLL cells. Finally, ectopic p27 expression in a CLL-derived cell line protects form cell death induced by fludarabine, which is consistent with the high p27 levels in this leukemia.
Descripción:	Resumen del póster presentado al First Symposium Neoplasbim - B-cell malignancies: from the bench to the patient, celebrado en Madrid del 23 al 24 de octubre de 2014.-- et al.
URI:	http://hdl.handle.net/10261/130701
Aparece en las colecciones:	(IBBTEC) Comunicaciones congresos