| RRC ID |
77840
|
| 著者 |
Taguchi T, Tsukuda M, Imagawa-Ishiguro Y, Kato Y, Sano D.
|
| タイトル |
Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib.
|
| ジャーナル |
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.
|
| 巻・号 |
19(1)
|
| ページ |
65-71
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
A431(RCB0202) |
