Toggle Main Menu Toggle Search

ePrints

The role of AP-1 in glucocorticoid resistance in leukaemia

Lookup NU author(s): Professor Simon Bailey, Emeritus Professor Andy Hall, Professor Andrew Pearson, Dr Chris Redfern

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


Abstract

Glucocorticoids are used in the treatment of acute lymphoblastic leukaemia (ALL) and chronic lymphocytic leukaemia (CLL) but many patients develop glucocorticoid resistance on relapse. The ligand-activated glucocorticoid receptor inhibits activity of the AP-1 transcription factor and the purpose of this study was to test the hypothesis that up-regulation or overexpression of AP1-binding activity may be an important mechanism of glucocorticoid resistance in ALL and CLL, In vitro sensitivity of patient blasts to prednisolone was measured using the MTT assay. AP-1 levels were quantified by gel shift analysis and Fos and Jun levels were compared by Western blotting. To test for a relationship between glucocorticoid sensitivity and glucocorticoid-induced changes in AP-1 binding activity, leukaemic blasts were also treated with prednisolone before analysis. Sensitivity of patient blasts to prednisolone varied, with IC50 values varying over a concentration range from 10(11) to 10(-4) M. Fos and Jun protein were detectable in all patient samples over a 300-fold range in relative expression, but did not correlate with prednisolone sensitivity. Gel-shift analysis demonstrated the presence of specific AP-1 -response-element-binding activity in all patient samples, but this did not correlate with prednisolone sensitivity. Furthermore, there was no relationship between prednisolone-induced changes in AP-1 binding activity and in vitro glucocorticoid resistance. These data show that glucocorticoid resistance is not associated with increased AP-1 binding activity or changes in the level of the Fos and Jun components of AP-1.


Publication metadata

Author(s): Bailey, S., Hall, A. G., Pearson, A. D. J., Redfern, C. P. F.

Publication type: Article

Publication status: Published

Journal: Leukemia

Year: 2001

Volume: 15

Issue: 3

Pages: 391-397

ISSN (print): 0887-6924

ISSN (electronic): 1476-5551

URL: http://dx.doi.org/10.1038/sj.leu.2402039

DOI: 10.1038/sj.leu.2402039

PubMed id: 11237062


Altmetrics

Altmetrics provided by Altmetric


Actions

    Link to this publication


Share