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Status |
Public on Apr 08, 2014 |
Title |
Genome-wide analysis of EGFR inhibitor erlotinib treatment in Head and neck, squamous cell carcinoma's FADU, SQ20B and Cal 27 |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by array
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Summary |
Chronic inflammation plays a significant role in tumor promotion, migration and invasion. Using microarray analysis, we observed a profound increase in genes involved in pro-inflammatory pathways in epidermal growth factor receptor inhibitor (EGFRI)-treated head and neck squamous cell carcinoma (HNSCC) cell lines compared to their respective vehicle-treated cell lines. We hypothesized that the efficacy of EGFRIs may be offset by the pro-inflammatory response that these drugs produce in HNSCC tumor cells. We found that clinical EGFRIs such as erlotinib, cetuximab, lapatinib and panitumumab induced the secretion of pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-8, GM-CSF, TNFα and IFNγ. Focusing on IL-6, we found that erlotinib induced a time-dependent increase in IL-6 mRNA and protein expression and exogenous IL-6 was able to protect HNSCC cells from erlotinib-induced cytotoxicity. Conversely, an IL-6 receptor antagonist tocilizumab, sensitized HNSCC cells to erlotinib in vitro and in vivo. Inhibitors of NFκB, p38 and JNK suppressed erlotinib-induced IL-6 expression, suggesting an important role of NFκB and MAPK pathways in IL-6 expression. Furthermore, knockdown of NADPH oxidase 4 (NOX4) suppressed erlotinib-induced pro-inflammatory cytokines expression. Taken together, these results suggest that clinical EGFRIs induce the expression of pro-inflammatory cytokines via NOX4. Therefore, the anti-tumor activity of EGFRIs may be partially reduced by activation of NOX4-mediated pro-inflammatory pathways in HNSCC.
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Overall design |
Total RNA was isolated from Head and Neck Squamous Cell Carcinoma cell lines FADU, SQ20B and Cal 27 subjected to 48 hours of 0.01% DMSO or 5uM EGFR inhibitor, erlotinib treatment.
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Contributor(s) |
Simons AL, Love-Homan L, Fletcher EV, Sobhakumari A, Feddersen CR, Goel A |
Citation(s) |
24048704 |
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Submission date |
Apr 09, 2013 |
Last update date |
Aug 13, 2018 |
Contact name |
Thomas B Bair |
E-mail(s) |
iihg-bioinformatics@uiowa.edu
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Organization name |
University of Iowa
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Street address |
335 EMRB
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City |
Iowa City |
State/province |
IA |
ZIP/Postal code |
52242 |
Country |
USA |
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Platforms (1) |
GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
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Samples (18)
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Relations |
BioProject |
PRJNA196596 |
Supplementary file |
Size |
Download |
File type/resource |
GSE45891_RAW.tar |
26.2 Mb |
(http)(custom) |
TAR |
GSE45891_non_normalized.txt.gz |
9.2 Mb |
(ftp)(http) |
TXT |
Processed data included within Sample table |
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