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Series GSE45891 Query DataSets for GSE45891
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
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.
 
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.
 
Contributor(s) Simons AL, Love-Homan L, Fletcher EV, Sobhakumari A, Feddersen CR, Goel A
Citation(s) 24048704
Submission date Apr 09, 2013
Last update date Aug 13, 2018
Contact name Thomas B Bair
E-mail(s) iihg-bioinformatics@uiowa.edu
Organization name University of Iowa
Street address 335 EMRB
City Iowa City
State/province IA
ZIP/Postal code 52242
Country USA
 
Platforms (1)
GPL10558 Illumina HumanHT-12 V4.0 expression beadchip
Samples (18)
GSM1119096 SQ20B 0.01% DMSO 48 hr-replicate 1
GSM1119097 SQ20B 0.01% DMSO 48 hr-replicate 2
GSM1119098 SQ20B 0.01% DMSO 48 hr-replicate 3
Relations
BioProject PRJNA196596

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

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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