Comparative analysis of gene expression profiles in lymphoma cells after treatment by Dexamethasone or CpdA

The project is directed to the development of selective glucocorticoid receptor agonists for anticancer therapy. Glucocorticoids (GC) are widely used in treatment of many types of cancer due to its ability to induce apoptosis in malignant cells (in blood cancer therapy) and to prevent nausea and emesis (in the chemotherapy of solid tumors). However, severe dose-limiting side effects occur, including osteoporosis, muscle wasting, diabetes and other metabolic complications. Both beneficial and harmful effects of glucocorticoids are due to selective activation or repression of particular genes by glucocorticoid receptor (GR). GR regulates gene expression via transactivation that requires GR homodimer binding to gene promoters and transrepression mediated via negative interaction between GR and other transcription factors as well as binding with negative glucocorticoid response elements (nGRE) in genes. GR transactivation is linked to metabolic side effects, while GR transrepression underlies glucocorticoid therapeutic action. Novel selective GR agonist Compound A (CpdA) prevents GR dimerization and transactivation, specifically activates GR transrepression, and has fewer side effects compared to glucocorticoids. Here we compare the gene expression profiles in lymphoma cells treated with glucocorticoid Dexamethasone (Dex) or CpdA B-cell mantle cell lymphoma cells Granta-519 were treated with Dexamethasone (1 uM), Compound A (1 uM) or solvent (Ethanol) for 16 h. Then cells were pelleted and total RNA was isolated with RiboPure kit (Ambion) according to manufacturer's protocol. The RNA samples were treated with TURBOTM DNase (Ambion). Quality control was performed with Agilent Bioanalyser.