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| Status |
Public on Feb 05, 2018 |
| Title |
BV6 induces an early wave of gene expression via NF-κB and AP-1 and a second wave via TNFα/TNFR1 signaling |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Smac mimetics are considered as promising cancer therapeutics, but little is yet known about how they alter gene expression. In this study we used an unbiased genome-wide expression array to investigate Smac mimetic BV6-induced gene regulation in breast cancer cell lines. Kinetic analysis revealed that BV6 alters gene expression in two waves. The first wave primarily involves NF-κB- and AP-1 families of transcription factors, while the second wave largely depends on tumor necrosis factor receptor 1 (TNFR1) signaling. Interestingly, disrupting auto-/paracrine tumor necrosis factor-α (TNFα)/ (TNFR1) signaling by knockdown of TNFR1 strongly attenuates the BV6-induced second wave of gene expression and upregulation of many pathways including NF-κB signaling, apoptosis and immune signalling, but not MAPK signaling pathways. Consistently, BV6 stimulates phosphorylation of cJun, a marker of MAPK cascade activation, irrespective of the presence or absence of the TNFα blocking antibody Enbrel. We show here in a comprehensive overview that BV6-induced gene expression in breast cancer cells takes place in a time- as well as TNFR1-dependent manner.
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| Overall design |
A total of 48 samples was analyzed. EVSA-T cells and MDA-MB-231 cells were transfected with control siRNA or siRNA directed at TNFR1 and then each of these conditions were treated with BV6 or left untreated. Samples were provided in duplicates for EVSA-T cells and triplicates for MDA-MB-231. Untransfected MDA-MB-231 were treated with BV6 for 3, 6, 9, 12, 15 hours in duplicates. Untreated controls were collected at 0, 9 and 15 hours in duplicates.
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| Contributor(s) |
Busch H, Boerries M, Fulda S, Schmidt N |
| Citation(s) |
29421152 |
| Submission date |
Dec 11, 2017 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Hauke Busch |
| E-mail(s) |
hauke.busch@uni-luebeck.de
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| Phone |
+49-451-3101-8470
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| Organization name |
University of Lübeck
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| Department |
Lübeck Institute of Experimental Dermatology
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| Street address |
Ratzeburger Allee 160
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| City |
Lübeck |
| State/province |
Schleswig-Holstein |
| ZIP/Postal code |
23538 |
| Country |
Germany |
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| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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| Samples (48)
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| Relations |
| BioProject |
PRJNA421923 |
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