Fig. 2: Glucocorticoid receptor (GR), induced by cisplatin, is a transcription factor of MAST1.
From: Cisplatin-mediated activation of glucocorticoid receptor induces platinum resistance via MAST1
a Transcriptional factor (TF) activation profiling identifies TFs whose activity is enhanced in KB-3-1 cells in response to cisplatin treatment. b MAST1 promoter activity in KB-3-1 lacking factors whose activity increased more than 1.8-fold by cisplatin. c Effect of GR or PR overexpression on MAST1 induction and cell viability in KB-3-1 cells treated with cisplatin. d ChIP assay of GR or PR binding to MAST1 promoter in KB-3-1 cells treated with cisplatin for the indicated times. e Comparison of MAST1 promoter activity in cells expressing WT or glucocorticoid response element (GRE)-mutated MAST1 promoter reporter. KB-3-1 cells were transfected with WT or GRE mutant MAST1 promoter reporter and treated with cisplatin. f Effect of GR knockdown or overexpression on MAST1 promoter activity in response to cisplatin treatment in KB-3-1 cells. g Effect of GR knockdown on MAST1 expression in KB-3-1 and A2780 cells in the presence or absence of cisplatin. h Comparison of MAST1 gene expression in TCGA OV patients stratified by GR-dependent gene signature expression monitoring gene expression of 47 glucocorticoid regulated genes. i Effect of chemotherapy agents on MAST1 promoter activity. KB-3-1 cells carrying MAST1 promoter were treated with sublethal doses of drugs (1 μg/ml cisplatin, 1 μM mitomycin C or camptothecin). j and k Induction of MAST1 by cisplatin and dexamethasone. KB-3-1 cells were treated with cisplatin (0.1, 0.2, 0.5 μg/ml), dexamethasone (100, 500 nM), or mifepristone (10 μΜ) for MAST1 promoter activity assay (j). GR antagonist mifepristone was used as a control. KB-3-1 and A2780 cells were treated with cisplatin (1 μg/ml), dexamethasone (500 nM), or combination for MAST1 protein induction (k). Data are mean ± SD from two technical replicates for a, three independent biological experiments for b–g and i–k. Statistical analyses were performed by two-tailed t-test for h and one-way ANOVA for the rest. Source data are provided as a Source Data file.
