Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies

// Dorien Clarisse 1, 2, 3 , Jonathan Thommis 1 , Karlien Van Wesemael 2, 4 , Rene Houtman 5 , Dariusz Ratman 1, 6 , Jan Tavernier 1, 3 , Fritz Offner 4 , Ilse Beck 2, 7, * and Karolien De Bosscher 1, 3, * 1 Receptor Research Laboratories, Nuclear Receptor Lab (NRL) and Cytokine Receptor Lab (CRL), VIB-UGent Center for Medical Biotechnology, Ghent University, Ghent, Belgium 2 Laboratory of Experimental Cancer Research (LECR), Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium 3 Cancer Research Institute Ghent (CRIG), Ghent, Belgium 4 Hematology, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium 5 PamGene International B.V., ‘s Hertogenbosch, The Netherlands 6 Current/Present address: Roche Global IT Solutions, Roche-Polska, Warsaw, Poland 7 Department of Health Sciences, Odisee University College, Ghent, Belgium * These authors have contributed equally to this work Correspondence to: Karolien De Bosscher, email: karolien.debosscher@vib-ugent.be Keywords: coregulator; glucocorticoid; glucocorticoid receptor; multiple myeloma; acute lymphoblastic leukemia Received: September 16, 2017     Accepted: November 14, 2017     Published: November 30, 2017 ABSTRACT Coregulators cooperate with nuclear receptors, such as the glucocorticoid receptor (GR), to enhance or repress transcription. These regulatory proteins are implicated in cancer, yet, their role in lymphoid malignancies, including multiple myeloma (MM) and acute lymphoblastic leukemia (ALL), is largely unknown. Here, we report the use and extension of the microarray assay for real-time nuclear receptor coregulator interactions (MARCoNI) technology to detect coregulator associations with endogenous GR in cell lysates. We use MARCoNI to determine the GR coregulator profile of glucocorticoid-sensitive (MM and ALL) and glucocorticoid-resistant (ALL) cells, and identify common and unique coregulators for different cell line comparisons. Overall, we identify SRC-1/2/3, PGC-1α, RIP140 and DAX-1 as the strongest interacting coregulators of GR in MM and ALL cells and show that the interaction strength does not correlate with GR protein levels. Lastly, as a step towards patient samples, we determine the GR coregulator profile of peripheral blood mononuclear cells. We profile the interactions between GR and coregulators in MM and ALL cells and suggest to further explore the GR coregulator profile in hematological patient samples.