HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib

  • Authors:
    • Jing Xu
    • Li Shen
    • Bi‑Cheng Zhang
    • Wen‑Hong Xu
    • Shu‑Qin Ruan
    • Chi Pan
    • Qi‑Chun Wei
  • View Affiliations

  • Published online on: November 9, 2016     https://doi.org/10.3892/ol.2016.5373
  • Pages: 5363-5369
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Abstract

Gefitinib is an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that has been demonstrated to be clinically useful for the treatment of patients with non‑small cell lung cancer (NSCLC). However, ~50% of patients do not respond to EGFR TKI treatment through the emergence of mutations, such as T790M. Therefore, it is important to determine which patients are eligible for treatment with gefitinib. As a preferred dimerization partner for EGFR, the role of EGFR 2 (HER2) in mediating sensitivity to gefitinib is poorly understood. In the present study, full‑length human HER2 cDNA was introduced to the NSCLC cell lines H1975 and H1299, which have a low endogenous expression level of HER2. In addition, it was observed in the present study that the H1975 cell line harbored the L858R and T790M mutations in the EGFR kinase domain. Western blot analysis and MTT assay were used to evaluate the TKI sensitivity of HER2 expression status, and the activation of HER3 and HER2 downstream effectors. The results indicated that the sensitivity of H1975 cells to gefitinib was restored by the overexpression of HER2, which stimulated HER2‑driven signaling cascades accompanied by the activation of protein kinase B. By contrast, ectopic HER2 overexpression in H1299 cells did not significantly alter the sensitivity to gefitinib treatment. In conclusion, the current study results suggested that the relatively resistance of the H1975 cell line to gefitinib could be reversed by the overexpression of HER2. Therefore, the expression of HER2 could also be considered when evaluate the patients' potential response to gefitinib, particularly in the subgroup of lung cancer patients who harbor an EGFR mutation.
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December-2016
Volume 12 Issue 6

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

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Spandidos Publications style
Xu J, Shen L, Zhang BC, Xu WH, Ruan SQ, Pan C and Wei QC: HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib. Oncol Lett 12: 5363-5369, 2016
APA
Xu, J., Shen, L., Zhang, B., Xu, W., Ruan, S., Pan, C., & Wei, Q. (2016). HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib. Oncology Letters, 12, 5363-5369. https://doi.org/10.3892/ol.2016.5373
MLA
Xu, J., Shen, L., Zhang, B., Xu, W., Ruan, S., Pan, C., Wei, Q."HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib". Oncology Letters 12.6 (2016): 5363-5369.
Chicago
Xu, J., Shen, L., Zhang, B., Xu, W., Ruan, S., Pan, C., Wei, Q."HER2 overexpression reverses the relative resistance of EGFR-mutant H1975 cell line to gefitinib". Oncology Letters 12, no. 6 (2016): 5363-5369. https://doi.org/10.3892/ol.2016.5373