Gefitinib-responsive EGFR-positive colorectal cancers have different proteome profiles from non-responsive cell lines
Gefitinib-responsive EGFR-positive colorectal cancers have different proteome profiles from non-responsive cell lines
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DOI：
10.1016/j.ejca.2005.06.014
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发表时间：
2005-10-01
影响因子：
8.4
通讯作者：
Zwierzina, H
中科院分区：
文献类型：
--
作者：
Loeffler-Ragg, J;Skvortsov, S;Zwierzina, H
预测对表皮生长因子受体（EGFR）酪氨酸激酶抑制剂治疗反应的生物标志物仍在很大程度上未表征。为了确定参与潜在耐药机制的蛋白质，我们研究了吉非替尼（ZD 1839，易瑞沙）在EGFR阳性结肠癌细胞系Caco-2，DiFi，HRT-18和HT-29中的作用。他们都没有表现出激活突变的EGFR外显子19或21。蛋白质组分析与二维聚丙烯酰胺凝胶电泳，然后质谱分析显示12个蛋白质差异表达的响应和非响应细胞。这些蛋白质参与代谢途径，与恶性生长部分相关，已知其中四种蛋白质与EGFR信号传导途径相互作用。泛素羧基终止水解酶同工酶L1（UCH-L1）和半乳糖凝集素-3在响应细胞系Caco-2中过表达，而脂肪酸结合蛋白（E-FABP）和热休克蛋白（hsp）27在耐药细胞系HRT-18和HT-29中表达更多，表明细胞对吉非替尼无响应性的作用。(c)2005爱思唯尔有限公司保留所有权利。
Biomarkers that predict response to therapy with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase remain largely uncharacterized. In order to define proteins involved in potential resistance mechanisms, we examined the effect of gefitinib (ZD1839, Iressa) in the EGFR-positive colon cancer cell lines Caco-2, DiFi, HRT-18 and HT-29. None of them exhibited an activating mutation in exons 19 or 21 of EGFR. Proteome profiling with two-dimensional polyacrylamide gel electrophoresis followed by mass spectrometry revealed 12 proteins differentially expressed in responsive and non-responsive cells. These proteins are involved in metabolic pathways, partially relevant in malignant growth and four of them are known to interact with the EGFR signalling pathway. Ubiquitin carboxyl-terminated hydrolase isozyme L1 (UCH-L1) and galectin-3 are overexpressed in the responsive cell line Caco-2, whereas fatty acid-binding protein (E-FABP) and heat shock protein (hsp) 27 are expressed more in the resistant cell lines HRT-18 and HT-29 suggesting a role in non-responsiveness of cells to gefitinib. (c) 2005 Elsevier Ltd. All rights reserved.