RRC ID 77840
Author Taguchi T, Tsukuda M, Imagawa-Ishiguro Y, Kato Y, Sano D.
Title Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib.
Journal Oncol Rep
Abstract Epidermal growth factor receptor (EGFR) gene mutations are associated with the sensitivity of non-small cell lung carcinomas (NSCLCs) to gefitinib, but such findings have not been reported in squamous cell carcinomas of the head and heck (SCCHNs). Accordingly, we determined whether EGFR gene expression and mutations correlate with the in vitro efficacy of gefitinib in SCCHN cell lines. EGFR status was analyzed in 16 different SCCHN cell lines by polymerase chain reaction (PCR) and direct sequencing for activating mutations, by real-time quantitative RT-PCR, and by Western blot analysis for RNA and protein expression. Using direct sequencing of PCR products from exons 18-23 of 9 SCCHN cell lines, we found a heterozygous EGFR mutation (EGFRmut) with a 2607Gright curved arrow A transition in exon 20 (G/A genotype). The 9 different cell lines that showed this mutation also showed higher sensitivity (lower IC50 values) to gefitinib than cell lines with wild-type EGFR (EGFRwt: G/G genotype) (p=0.016). EGFR protein levels correlated robustly (r=0.76) and significantly (p=0.0007) with EGFR mRNA levels and with IC50 values for gefitinib (r=0.65, p=0.0067). EGFR mRNA correlated with IC50 values (r=0.67, p=0.0046). Our conclusion was that the heterozygous and synonymous transition of the EGFR gene and low EGFR expression levels of mRNA and protein in SCCHN may be reliable predictors of high sensitivity in SCCHN patients to gefitinib.
Volume 19(1)
Pages 65-71
Published 2008-1-1
PMID 18097577
MeSH Antineoplastic Agents / pharmacology* Base Sequence Blotting, Western Carcinoma, Squamous Cell / drug therapy Carcinoma, Squamous Cell / genetics* Cell Line, Tumor Cell Proliferation / drug effects Drug Resistance, Neoplasm / genetics ErbB Receptors / genetics* Gefitinib Gene Expression Head and Neck Neoplasms / drug therapy Head and Neck Neoplasms / genetics* Humans Inhibitory Concentration 50 Molecular Sequence Data Mutation Quinazolines / pharmacology* RNA, Messenger / analysis Reverse Transcriptase Polymerase Chain Reaction
IF 3.417
Human and Animal Cells A431(RCB0202)