Coregulator Profiling of the Glucocorticoid Receptor in Lymphoid Malignancies

Overview

Journal Oncotarget

Specialty Oncology

Date 2018 Jan 10

PMID 29312638

Citations 9

Authors

Dorien Clarisse

Jonathan Thommis

Karlien Van Wesemael

Rene Houtman

Dariusz Ratman

Jan Tavernier

Fritz Offner

Ilse Beck

Karolien De Bosscher

Affiliations

Soon will be listed here.

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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