GSE200313 Exploiting crosstalk between glucocorticoid and mineralocorticoid receptors enhances glucocorticoid-induced killing of multiple myeloma cells

Contributors : Dorien Clarisse ; Philip Vlummens ; Karlien Van Wesemael ; Jonathan Thommis ; Daria Fijalkowska ; Guillaume Acke ; lse M Beck ; Fritz Offner ; Karolien De BosscherSeries Type : Expression profiling by high throughput sequencingOrganism : Homo sapiensLong-term glucocorticoid treatment in multiple myeloma is hampered by deleterious side effects. Glucocorticoids bind to the glucocorticoid receptor (GR), which is a crucial drug target because its activation triggers myeloma cell death. The mineralocorticoid receptor (MR) is a closely related nuclear receptor but its impact on glucocorticoid responsiveness in myeloma is unknown. Here we reveal a functional crosstalk between GR and MR that culminates in improved myeloma cell killing. We show that the GR agonist Dexamethasone (Dex) downregulates MR levels in a GR-dependent way in myeloma cells. Co-treatment of Dex with the MR antagonist Spironolactone enhances Dex-induced cell killing in (primary) myeloma cells. The crosstalk is further evidenced by an endogenous interaction between GR and MR in myeloma cells that is ligand-inducible and by a distinctive gene expression profile. Our study demonstrates that GR-MR crosstalk is therapeutically relevant in myeloma and presents a glucocorticoid-based dose-reduction strategy that could diminish glucocorticoid-related side effects in patients.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research