A novel PDGFRA mutation in gastrointestinal stromal tumours, L839P, is sensitive to imatinib in vitro

  • Authors:
    • Chenguang Bai
    • Xiaohong Liu
    • Jian-Ming Zheng
    • Cen  Qiu
    • Yan Zhu
    • Jingjing Xu
    • Jing Zhao
    • Dalie Ma
  • View Affiliations

  • Published online on: February 10, 2012     https://doi.org/10.3892/ol.2012.599
  • Pages: 1139-1143
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Abstract

Evidence suggests that different types of mutation in gastrointestinal stromal tumours (GISTs) correlate with different response rates to imatinib (Glivec, STI571). The purpose of this study was to explore the sensitivity of the PDGFRAL839P mutant, a novel gain-of-function mutation isoform related to GISTs, to imatinib in vitro. The eukaryotic expression vectors pcDNA3.1-PDGFRAWild, pcDNA3.1-PDGFRAD842V and pcDNA3.1-PDGFRAL839P were constructed and transfected into Chinese hamster ovary (CHO) cells by liposome methods. The responses of cells with PDGFRAWild, PDGFRAL839P and PDGFRAD842V mutants to imatinib were determined by methyl thiazolyl tetrazolium (MTT) assay, western blotting and apoptosis assays. Reults of the MTT assay revealed that the growth rate of CHO(PDGFRAL839P) cells decreased to approximately 60% when exposed to 1 µM imatinib and to approximately 50% with 5 µM imatinib. However, the growth rate of CHO(PDGFRAD842V) cells did not significantly change with 5 µM imatinib. Western blot analysis indicated that 1 µM imatinib completely blocked the phosphorylation of PDGFRAL839P, but did not affect PDGFRAD842V phosphorylation. Apoptosis analysis suggested that the percentage of apoptotic CHO(PDGFRAL839P) cells increased approximately 4-fold (from 5.90 to 25.2%) with 1 µM imatinib. Although the treatment of CHO(PDGFRAD842V) and CHO(PDGFRAWild) cells with 5 µM imatinib resulted in a slight increase in the number of apoptotic cells, the percentage of apoptotic cells remained approximately 10% of the total population. Our findings showed that the PDGFRA gene mutation isoform L839P is sensitive to inhibition by imatinib. Screening for PDGFRA mutations in GISTs is essential to identify the response to treatment with imatinib.
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May 2012
Volume 3 Issue 5

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Bai C, Liu X, Zheng J, Qiu C, Zhu Y, Xu J, Zhao J and Ma D: A novel PDGFRA mutation in gastrointestinal stromal tumours, L839P, is sensitive to imatinib in vitro. Oncol Lett 3: 1139-1143, 2012
APA
Bai, C., Liu, X., Zheng, J., Qiu, C., Zhu, Y., Xu, J. ... Ma, D. (2012). A novel PDGFRA mutation in gastrointestinal stromal tumours, L839P, is sensitive to imatinib in vitro. Oncology Letters, 3, 1139-1143. https://doi.org/10.3892/ol.2012.599
MLA
Bai, C., Liu, X., Zheng, J., Qiu, C., Zhu, Y., Xu, J., Zhao, J., Ma, D."A novel PDGFRA mutation in gastrointestinal stromal tumours, L839P, is sensitive to imatinib in vitro". Oncology Letters 3.5 (2012): 1139-1143.
Chicago
Bai, C., Liu, X., Zheng, J., Qiu, C., Zhu, Y., Xu, J., Zhao, J., Ma, D."A novel PDGFRA mutation in gastrointestinal stromal tumours, L839P, is sensitive to imatinib in vitro". Oncology Letters 3, no. 5 (2012): 1139-1143. https://doi.org/10.3892/ol.2012.599