期刊文献+

人肺癌EGFR基因突变与Gefitinib耐药相关性研究 被引量:6

Relationship between Mutations of the Epidermal Growth Factor Receptor Gene and Drug-Resistance to Gefitinib in Human Lung Cancer in vitro
下载PDF
导出
摘要 背景与目的以人肺癌细胞株PC9及其耐药子系细胞PC9/AB2、PC9/AB11、PC9/BB4为模型,观察4株细胞对Gefitinib的耐药差异及耐药机制。方法体外培养细胞测定耐药指数,对4株细胞EGFR基因exon18-21进行测序并在mRNA水平上的测定表达量差异。结果PC9及其3株耐药子系细胞均存在耐药性差异。PC9及其3株耐药子系细胞均存在19外显子15bp缺失突变并且耐药细胞株PC9/AB11外显子20存在A→G的点突变。敏感细胞株PC9的EGFR基因在mRNA水平上的表达量明显高于其他3株耐药株。结论PC9、PC9/AB2、PC9/AB11和PC9/BB4肺癌细胞株对Gefitinib的耐药性存在非常显著的差异,4株肺癌细胞株EGFR基因突变和mRNA表达水平的差异与其与Gefitinib获得性耐药有关。 Background and objective To explore cell lines' difference of drug-resistance to gefitinib and the underlying mechanism. Methods Human lung cancer cell lines of PC9, PC9/AB2, PC9/AB11, PC9/BB4 were treated in vitro, exons 18-21 of EGFR gene were sequenced and EGFR gene mRNA levels were measured. Results Four cell lines' drug resistance difference of gefitinib were validated. All the four cell lines had the 15 bp deletion at exon 19, and AB11 had A to G point-mutation at exon 20. PC9 EGFR gene in the sensitive cell line was expressed much higher than that in 3 resistance cell lines by real-time PCR. Conclusion There is significant difference of drug-resistance to gefitinib existed among the lung cancer cell lines PC9, PC9/AB2, PC9/AB 11 and PC9/BB4. The mutations changes of expressive level of EGFR gene might be correlated with the acquired drug-resistance to gefitinib in lung cancer cell lines.
出处 《中国肺癌杂志》 CAS 2009年第1期28-32,共5页 Chinese Journal of Lung Cancer
基金 国家863重大项目(No.2006AA02A401) 科技部国家合作重大项目攻关(No.2006DFB32330) 国家“十一五”科技攻关项目(No.2006BAI02A01)资助~~
关键词 EGFR基因 耐药 GEFITINIB 肺肿瘤 EGFR genes Resistance Gefitinib Lung neoplasms
  • 相关文献

二级参考文献19

  • 1Minna JD, Gazdar AF, Sprang SR, Herz J. Cancer. A bull's eye for targeted lung cancer therapy. Science 2004; 304:1458-61. 被引量:1
  • 2Dowell JE, Minna JD. Chasing mutations in the epidermal growth factor in lung cancer. N Engl J Med 2005; 352:830-2. 被引量:1
  • 3Tanovic A, Alfaro V. Gefitinib: current status in the treatment of non-small cell lung cancer. Drugs Today (Barc) 2004; 40:809-27. 被引量:1
  • 4Ross JS, Schenkein DP, Pietrusko R, et al. Targeted therapies for cancer 2004. Am J Clin Pathol 2004; 122:598-609. 被引量:1
  • 5Paez JG, Janne PA, Lee JC, et al. EGFR mutations in lung cancer:correlation with clinical response to gefitinib therapy. Science2004; 304:1497-500. 被引量:1
  • 6Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N Engl J Med 2004; 350:2129-39. 被引量:1
  • 7Huang SF, Liu HP, Li LH, et al. High frequency of epidermal growth factor receptor mutations with complex patterns in nonsmall cell lung cancers related to gefitinib responsiveness in Taiwan. Clin Cancer Res 2004; 10:8195-203. 被引量:1
  • 8Han SW, Kim TY, Hwang PG, et al. Predictive and Prognostic Impact of Epidermal Growth Factor Receptor Mutation in NonSmall-Cell Lung Cancer Patients Treated With Gefitinib. J Clin Oncol 2005; Feb 14: Epub ahead of print. http://dx.doi.org/10.1200/JCO.2005.01.388. 被引量:1
  • 9Kosaka T, Yatabe Y, Endoh H, et al. Mutations of the epidermal growth factor receptor gene in lung cancer: biological and clinical implications. Cancer Res 2004; 64:8919-23. 被引量:1
  • 10Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological features associated with epidermal growth factor receptor gene mutations in lung cancers. J Natl Cancer Inst 2005; 97:339-46. 被引量:1

共引文献66

同被引文献37

引证文献6

二级引证文献22

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部