E-GEOD-41062 - Expression of DND41 cell lines treated with 1µM Dexamethasone for 24h after shPTEN infection
Released on 1 October 2013, last updated on 2 June 2014
Glucocorticoid resistance is a major driver of therapeutic failure in T-cell acute lymphoblastic leukemia (T-ALL). Here we identify the AKT1 kinase as a signaling factor driving glucocorticoid resistance in T-ALL. Mechanistically, AKT1 directly phosphorylates the glucocorticoid receptor NR3C1 protein and blocks glucocorticoid-induced NR3C1 transcription by inhibiting glucocorticoid-induced NT3C1 translocation to the nucleus. Consistently, pharmacologic inhibition of AKT1 increases the response of T-ALL cells to glucocorticoid therapy and effectively reverses glucocorticoid resistance in vitro and in vivo. These results warrant the clinical testing of AKT1 inhibitors and glucocorticoids in combination for the treatment of T-ALL. Gene Expression Analysis of DND41 cell lines infected with shPTEN or shLUC and treated with 1µM Dexamethasone vs DMSO for 24h, in triplicate.
transcription profiling by array
Adolfo A Ferrando, Alberto Ambesi-Impiombato