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Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies

Dorien Clarisse (UGent) , Jonathan Thommis (UGent) , Karlien Van Wesemael (UGent) , Rene Houtman, Dariusz Ratman (UGent) , Jan Tavernier (UGent) , Fritz Offner (UGent) , Ilse Beck (UGent) and Karolien De Bosscher (UGent)
(2017) ONCOTARGET. 8(65). p.109675-109691
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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-1 alpha, 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.
Keywords
BREAST-CANCER, TRANSCRIPTIONAL COREGULATORS, THERAPEUTIC TARGETS, GENE-EXPRESSION, COACTIVATORS, DISEASE, CELLS, MECHANISMS, HEALTH, RESISTANT, coregulator, glucocorticoid, glucocorticoid receptor, multiple myeloma, acute lymphoblastic leukemia

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Chicago
Clarisse, Dorien, Jonathan Thommis, Karlien Van Wesemael, Rene Houtman, Dariusz Ratman, Jan Tavernier, Fritz Offner, Ilse Beck, and Karolien De Bosscher. 2017. “Coregulator Profiling of the Glucocorticoid Receptor in Lymphoid Malignancies.” Oncotarget 8 (65): 109675–109691.
APA
Clarisse, D., Thommis, J., Van Wesemael, K., Houtman, R., Ratman, D., Tavernier, J., Offner, F., et al. (2017). Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies. ONCOTARGET, 8(65), 109675–109691.
Vancouver
1.
Clarisse D, Thommis J, Van Wesemael K, Houtman R, Ratman D, Tavernier J, et al. Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies. ONCOTARGET. 2017;8(65):109675–91.
MLA
Clarisse, Dorien, Jonathan Thommis, Karlien Van Wesemael, et al. “Coregulator Profiling of the Glucocorticoid Receptor in Lymphoid Malignancies.” ONCOTARGET 8.65 (2017): 109675–109691. Print.
@article{8549647,
  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-1 alpha, 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.},
  author       = {Clarisse, Dorien and Thommis, Jonathan and Van Wesemael, Karlien and Houtman, Rene and Ratman, Dariusz and Tavernier, Jan and Offner, Fritz and Beck, Ilse and De Bosscher, Karolien},
  issn         = {1949-2553},
  journal      = {ONCOTARGET},
  language     = {eng},
  number       = {65},
  pages        = {109675--109691},
  title        = {Coregulator profiling of the glucocorticoid receptor in lymphoid malignancies},
  url          = {http://dx.doi.org/10.18632/oncotarget.22764},
  volume       = {8},
  year         = {2017},
}

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