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Series GSE66837 Query DataSets for GSE66837
Status Public on Mar 13, 2015
Title The oncogene EVI1 enhances transcriptional and biological responses of human myeloid cells to all-trans retinoic acid [HL60]
Organism Homo sapiens
Experiment type Expression profiling by array
Summary The product of the ecotropic virus integration site 1 (EVI1) gene, whose overexpression is associated with a poor prognosis in myeloid leukemias and some epithelial tumors, regulates gene transcription both through direct DNA binding and through modulation of the activity of other sequence specific transcription factors. Previous results from our laboratory have shown that EVI1 influenced transcription regulation in response to the myeloid differentiation inducing agent, all-trans retinoic acid (ATRA), in a dual manner: it enhanced ATRA induced transcription of the RARb gene, but repressed the ATRA induction of the EVI1 gene itself. In the present study, we asked whether EVI1 would modulate the ATRA regulation of a larger number of genes, as well as biological responses to this agent, in human myeloid cells. U937 and HL-60 cells ectopically expressing EVI1 through retroviral transduction were subjected to microarray based gene expression analysis, and to assays measuring cellular proliferation, differentiation, and apoptosis. These experiments showed that EVI1 modulated the ATRA response of several dozens of genes, and in fact reinforced it in the vast majority of cases. A particularly strong synergy between EVI1 and ATRA was observed for GDF15, which codes for a member of the TGF-b superfamily of cytokines. In line with the gene expression results, EVI1 enhanced cell cycle arrest, differentiation, and apoptosis in response to ATRA, and knockdown of GDF15 counteracted some of these effects.
Overall design HL60 cells transduced with an EVI1 expression vector or empty vector as a control were treated with all-trans retinoic acid (ATRA) or an equivalent amount of DMSO (solvent) for 24 h prior to gene expression microarray analysis. 3 biological replicates were performed.
Contributor(s) Steinmetz B, Hackl H, Wieser R
Citation(s) 25486480, 26036413
Submission date Mar 12, 2015
Last update date Oct 09, 2019
Contact name Rotraud Wieser
Organization name Medical University of Vienna
Department Clinic of Medicine I
Street address Waehringer Guertel 18-20
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (1)
GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array
Samples (12)
GSM1633063 HL60_vec DMSO replicate 1
GSM1633064 HL60_EVI1 DMSO replicate 1
GSM1633065 HL60_vec ATRA replicate 1
BioProject PRJNA278064

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Supplementary file Size Download File type/resource
GSE66837_RAW.tar 55.0 Mb (http)(custom) TAR (of CEL)
Raw data provided as supplementary file
Processed data included within Sample table

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