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AURKA upregulation plays a role in fibroblast-reduced gefitinib sensitivity in the NSCLC cell line HCC827
- Source :
- Oncology Reports
- Publication Year :
- 2015
- Publisher :
- Spandidos Publications, 2015.
-
Abstract
- Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (EGFR-TKIs) have been used to treat non-small cell lung carcinoma (NSCLC) patients that have EGFR-activating mutations. EGFR-TKI monotherapy in most NSCLC patients with EGFR mutations who initially respond to EGFR-TKIs results in the development of acquired resistance. We investigated the role of fibroblasts in stromal cell-mediated resistance to gefitinib-induced apoptosis in EGFR-mutant NSCLC cells. While gefitinib induced apoptosis in EGFR-mutant NSCLC cells, apoptosis induction was diminished under stromal co-culture conditions. Protection appeared to be mediated in part by Aurora-A kinase (AURKA) upregulation. The protective effect of stromal cells was significantly reduced by pre-exposure to AURKA-shRNA. We suggest that combinations of AURKA antagonists and EGFR inhibitors may be effective in clinical trials targeting mutant EGFR NSCLCs.
- Subjects :
- Cancer Research
Lung Neoplasms
Stromal cell
Recombinant Fusion Proteins
gefitinib
Antineoplastic Agents
NSCLC
resistance
Gefitinib
Downregulation and upregulation
Carcinoma, Non-Small-Cell Lung
Cell Line, Tumor
fibroblasts
medicine
Humans
Gene Regulatory Networks
Epidermal growth factor receptor
RNA, Small Interfering
Protein Kinase Inhibitors
Aurora Kinase A
EGFR inhibitors
biology
Proto-Oncogene Proteins c-mdm2
Genes, erbB-1
Articles
General Medicine
Cell cycle
Coculture Techniques
Neoplasm Proteins
Up-Regulation
respiratory tract diseases
ErbB Receptors
Gene Expression Regulation, Neoplastic
Oncology
Drug Resistance, Neoplasm
Enzyme Induction
Quinazolines
Cancer research
biology.protein
RNA Interference
Stromal Cells
Tumor Suppressor Protein p53
Signal transduction
Aurora-A kinase
Tyrosine kinase
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 17912431 and 1021335X
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Oncology Reports
- Accession number :
- edsair.doi.dedup.....12e129bb091e8a6c1f92fed1cddf2b5e