Differential regulation of the human MRP2 and MRP3 gene expression by glucocorticoids

A549 cells (non-small-cell lung cancer cell line) were challenged with glucocorticoids (dexamethasone, hydrocortisone and prednisone) at physiologically and therapeutically relevant concentrations for 24 h and changes in MRP2 and MRP3 expression were followed on four levels: promoter regulation (luciferase reporter constructs), mRNA level (semi-quantitative real-time PCR), protein level (Western blotting) and activity (drug resistance and cellular transport of the model substrate calcein). DEX and HCT in the submicromolar concentration range caused a 2-fold induction of transcriptional activity at the MRP3 promoter construct, while MRP2 expression was not activated. All investigated glucocorticoids caused a modest stimulation of organic anion transport activity. We conclude that glucocorticoids used in clinical practice have the ability to transcriptionally upregulate human MRP3 gene expression in lung-derived cells where this protein is a major component of the organic anion extrusion system. This phenomenon has to be taken into account when designing treatments for lung cancer, especially for patients treated simultaneously with glucocorticoids against inflammatory symptoms.