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Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies.

Authors
  • Clarisse, Dorien1, 2, 3
  • Thommis, Jonathan1
  • Van Wesemael, Karlien2, 4
  • Houtman, René5
  • Ratman, Dariusz1, 6
  • Tavernier, Jan1, 3
  • Offner, Fritz4
  • Beck, Ilse2, 7
  • De Bosscher, Karolien1, 3
  • 1 Receptor Research Laboratories, Nuclear Receptor Lab (NRL) and Cytokine Receptor Lab (CRL), VIB-UGent Center for Medical Biotechnology, Ghent University, Ghent, Belgium. , (Belgium)
  • 2 Laboratory of Experimental Cancer Research (LECR), Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium. , (Belgium)
  • 3 Cancer Research Institute Ghent (CRIG), Ghent, Belgium. , (Belgium)
  • 4 Hematology, Department of Internal Medicine, Ghent University Hospital, Ghent, Belgium. , (Belgium)
  • 5 PamGene International B.V., 's Hertogenbosch, The Netherlands. , (Netherlands)
  • 6 Current/Present address: Roche Global IT Solutions, Roche-Polska, Warsaw, Poland. , (Poland)
  • 7 Department of Health Sciences, Odisee University College, Ghent, Belgium. , (Belgium)
Type
Published Article
Journal
Oncotarget
Publisher
"Impact Journals, LLC "
Publication Date
Dec 12, 2017
Volume
8
Issue
65
Pages
109675–109691
Identifiers
DOI: 10.18632/oncotarget.22764
PMID: 29312638
Source
Medline
Keywords
License
Unknown

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.

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