Clarisse Dorien, Thommis Jonathan, Van Wesemael Karlien, Houtman René, Ratman Dariusz, Tavernier Jan, Offner Fritz, Beck Ilse, De Bosscher Karolien
Receptor Research Laboratories, Nuclear Receptor Lab (NRL) and Cytokine Receptor Lab (CRL), VIB-UGent Center for Medical Biotechnology, Ghent University, Ghent, Belgium.
Laboratory of Experimental Cancer Research (LECR), Department of Radiation Oncology and Experimental Cancer Research, Ghent University, Ghent, Belgium.
Oncotarget. 2017 Nov 30;8(65):109675-109691. doi: 10.18632/oncotarget.22764. eCollection 2017 Dec 12.
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.
共调节因子与核受体（如糖皮质激素受体（GR））协同作用，以增强或抑制转录。这些调节蛋白与癌症有关，然而，它们在包括多发性骨髓瘤（MM）和急性淋巴细胞白血病（ALL）在内的淋巴系统恶性肿瘤中的作用在很大程度上尚不清楚。在这里，我们报告了用于实时核受体共调节因子相互作用（MARCoNI）技术的微阵列分析方法的应用和扩展，以检测细胞裂解物中与内源性GR相关的共调节因子。我们使用MARCoNI来确定糖皮质激素敏感（MM和ALL）和糖皮质激素耐药（ALL）细胞的GR共调节因子谱，并识别不同细胞系比较中的共同和独特的共调节因子。总体而言，我们确定SRC-1/2/3、PGC-1α、RIP140和DAX-1是MM和ALL细胞中GR最强的相互作用共调节因子，并表明相互作用强度与GR蛋白水平无关。最后，作为迈向患者样本研究的一步，我们确定了外周血单个核细胞的GR共调节因子谱。我们分析了MM和ALL细胞中GR与共调节因子之间的相互作用，并建议进一步探索血液学患者样本中的GR共调节因子谱。
