Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib.
Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib.
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DOI：
10.3892/or.19.1.65
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发表时间：
2008
期刊：
影响因子：
4.2
通讯作者：
T. Taguchi;M. Tsukuda;Yukari Imagawa-Ishiguro;Y. Kato;D. Sano
中科院分区：
文献类型：
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作者：
T. Taguchi;M. Tsukuda;Yukari Imagawa-Ishiguro;Y. Kato;D. Sano
表皮生长因子受体（EGFR）基因突变与非小细胞肺癌（NSCLC）对吉非替尼的敏感性相关，但在头颈部鳞状细胞癌（SCCHN）中尚未报道此类发现。因此，我们确定EGFR基因表达和突变是否与吉非替尼在SCCHN细胞系中的体外疗效相关。EGFR的状态进行了分析，在16个不同的SCCHN细胞系通过聚合酶链反应（PCR）和直接测序的激活突变，通过实时定量RT-PCR，并通过蛋白质印迹分析的RNA和蛋白质表达。对9个SCCHN细胞株的18-23号外显子PCR产物进行直接测序，发现EGFR基因20号外显子存在一个2607 G右箭头A突变的杂合突变（EGFRmut）（G/A基因型）。显示该突变的9种不同细胞系对吉非替尼的敏感性（较低的IC 50值）也高于具有野生型EGFR（EGFRwt：G/G基因型）的细胞系（p=0.016）。EGFR蛋白水平与EGFR mRNA水平和吉非替尼的IC 50值（r = 0.65，p= 0.0067）具有稳健（r =0.76）和显著（p = 0.0007）相关性。EGFR mRNA与IC 50值相关（r=0.67，p=0.0046）。我们的结论是，EGFR基因的杂合和同义转换和低EGFR表达水平的mRNA和蛋白在SCCHN可能是可靠的预测SCCHN患者对吉非替尼的高敏感性。
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.