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| Status |
Public on Mar 10, 2015 |
| Title |
Gene expression changes in U937 cells in response to ectopic expression of EVI1 and/or etoposide treatment |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Overexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). Similarly, inducible expression of EVI1 in HL-60 cells decreased their sensitivity to daunorubicin. Gene expression microarray analyses of U937_EVI1 and U937_vec cells cultured in the absence or presence of etoposide showed that 77 and 419 genes were regulated by EVI1 and etoposide, respectively. Notably, mRNA levels of 26 of these genes were altered by both stimuli, indicating that EVI1 regulated genes were strongly enriched among etoposide regulated genes and vice versa. One of the genes that were induced by both EVI1 and etoposide was CDKN1A/p21/WAF, which in addition to its function as a cell cycle regulator plays an important role in conferring chemotherapy resistance in various tumor types. Indeed, overexpression of CDKN1A in U937 cells mimicked the phenotype of EVI1 overexpression, similarly conferring partial resistance to antileukemic drugs.
Rommer A, Steinmetz B, Herbst F, Hackl H, Heffeter P, Heilos D, Filipits M, Steinleitner K, Hemmati S, Herbacek I, Schwarzinger I, Hartl K, Rondou P, Glimm H, Karakaya K, Krämer A, Berger W, and Wieser R: EVI1 Inhibits Apoptosis Induced by Antileukemic Drugs via Upregulation of CDKN1A/p21/WAF in Human Myeloid Cells. PLoS One 8(2):e56308 (2013). doi: 10.1371/journal.pone.0056308.
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| Overall design |
U937 cells transduced with an EVI1 expression vector or empty vector as control were treated or not with 400 nM etoposide for 48h. 2 biological replicate experiments were performed.
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| Contributor(s) |
Rommer A, Hackl H, Wieser R |
| Citation(s) |
23457546 |
| Submission date |
Mar 09, 2015 |
| Last update date |
Nov 08, 2016 |
| Contact name |
Rotraud Wieser |
| E-mail(s) |
rotraud.wieser@meduniwien.ac.at
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| Organization name |
Medical University of Vienna
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| Department |
Clinic of Medicine I
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| Street address |
Waehringer Guertel 18-20
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| City |
Vienna |
| ZIP/Postal code |
1090 |
| Country |
Austria |
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| Platforms (1) |
| GPL11532 |
[HuGene-1_1-st] Affymetrix Human Gene 1.1 ST Array [transcript (gene) version] |
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| Samples (8)
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| GSM1627261 |
U937_vec cells, etoposide treatment, biological replicate 1 |
| GSM1627262 |
U937_vec cells, control, biological replicate 1 |
| GSM1627263 |
U937_EVI1 cells, etoposide treatment, biological replicate 1 |
| GSM1627264 |
U937_EVI1 cells, control, biological replicate 1 |
| GSM1627265 |
U937_vec cells, etoposide treatment, biological replicate 2 |
| GSM1627266 |
U937_vec cells, control, biological replicate 2 |
| GSM1627267 |
U937_EVI1 cells, etoposide treatment, biological replicate 2 |
| GSM1627268 |
U937_EVI1 cells, control, biological replicate 2 |
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| Relations |
| BioProject |
PRJNA277699 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE66660_RAW.tar |
36.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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