Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib.
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.
Taguchi
Takahide
T
Department of Otorhinolaryngology and Head and Neck Surgery, Yokohama City University School of Medicine, Yokohama 236-0004, Japan. ttaguchi@yokohama-cu.ac.jp
Tsukuda
Mamoru
M
Imagawa-Ishiguro
Yukari
Y
Kato
Yasumasa
Y
Sano
Daisuke
D
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D000077156:Gefitinib; D015870:Gene Expression; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D008969:Molecular Sequence Data; D009154:Mutation; D011799:Quinazolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000970:Antineoplastic Agents; D011799:Quinazolines; D012333:RNA, Messenger; D066246:ErbB Receptors; D000077156:Gefitinib