Mutations of the epidermal growth factor receptor gene in gastrointestinal tract tumor cell lines.
Mutations of the epidermal growth factor receptor gene in gastrointestinal tract tumor cell lines.
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DOI：
10.3892/or.15.5.1205
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发表时间：
2006-05
期刊：
影响因子：
4.2
通讯作者：
Toshimoto Kimura;C. Maesawa;K. Ikeda;G. Wakabayashi;T. Masuda
中科院分区：
文献类型：
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作者：
Toshimoto Kimura;C. Maesawa;K. Ikeda;G. Wakabayashi;T. Masuda
表皮生长因子受体(EGFR)在许多人类肿瘤中普遍过表达，包括胃肠道肿瘤。吉非替尼是EGFR酪氨酸激酶的选择性抑制剂，可阻断多种信号转导通路，包括参与肿瘤细胞增殖、血管生成和转移的信号转导通路。最近的突变和生物学研究表明，EGFR基因酪氨酸激酶域的突变与吉非替尼的疗效密切相关，这些突变经常出现在影响女性、东亚人和非吸烟者的非小细胞肺癌中。这导致我们推测EGFR基因突变可能在胃肠道癌(GITCs)中频繁发生，因为在这些类型的肿瘤中观察到过表达。为了研究GICT中的EGFR突变，我们研究了11个食道癌、6个胃癌和12个结直肠癌细胞系。我们在一个胃癌细胞系中发现了一个错义突变，并发现了10个单核苷酸多态。EGFR基因酪氨酸激酶域的罕见突变表明，吉非替尼作为GITC的单一药物治疗不太可能可靠。
The epidermal growth factor receptor (EGFR) is commonly overexpressed in many human tumors including gastrointestinal tract tumors. Gefitinib is a selective inhibitor of EGFR tyrosine kinase, and blocks several signal transduction pathways including those involved in tumor cell proliferation, angiogenesis and metastasis. Recent mutational and biological studies have suggested that mutations in the tyrosine kinase domain of the EGFR gene are well correlated with the response to gefitinib, and that these mutations are frequently observed in non-small cell lung cancers affecting women, East Asians and non-smokers. This led us to speculate that EGFR gene mutations may occur frequently in gastrointestinal tract carcinomas (GITCs) because overexpression is observed in these tumor types. To investigate EGFR mutations in GICTs, we studied 11 esophageal, 6 gastric, and 12 colorectal cancer cell lines. We found a missense mutation in a gastric cancer cell line, and 10 single nucleotide polymorphisms. The occurrence of rare mutations in the tyrosine kinase domain of the EGFR gene suggests that gefitinib is unlikely to be reliable as single-drug therapy for GITCs.