Lookup NU author(s): Dr Lindsay Nicholson,
Emeritus Professor Andy Hall,
Dr Chris Redfern,
Professor Julie Irving
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Glucocorticoids (GCs) are pivotal agents in the treatment of childhood acute lymphoblastic leukaemia (ALL) but the molecular basis of GC-resistance remains unclear. Expression-array studies have shown that commonly upregulated genes associated with GC-sensitivity include GR, glucocorticoid-induced leucine zipper (GILZ) and I kappa B alpha, which all negatively interact with components of the pro-survival NF kappa B pathway and therefore may be critical determinants of GC-sensitivity. We have investigated these regulators and their effect on NF kappa B activity in GC-resistant descendents of the B-lineage ALL cell line, PreB 697. We show that while differential up regulation of the modulators (GILZ, GR and I kappa B alpha) was demonstrated in GC-sensitive compared to GC-resistant sub-lines, this was not coupled with altered nuclear translocation or functionality of the RelA, p50 or c-Rel subunits of NF kappa B. Thus, GC-resistance in the PreB 697 cell line model is not mediated by NF kappa B, however further investigation of the impact of these GC-sensitive associated proteins on other survival pathways, such as the RAS-RAF-MEK-ERK pathway, is warranted. (C) 2010 Elsevier Ltd. All rights reserved.
Author(s): Nicholson L, Hall AG, Redfern CP, Irving J
Publication type: Article
Publication status: Published
Journal: Leukemia Research
Print publication date: 01/10/2010
ISSN (print): 0145-2126
ISSN (electronic): 1873-5835
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