Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells

  • Authors:
    • Sangmin Kim
    • Jeongmin Lee
    • Soo Jin Oh
    • Seok Jin Nam
    • Jeong Eon Lee
  • View Affiliations

  • Published online on: July 8, 2015     https://doi.org/10.3892/or.2015.4116
  • Pages: 1613-1619
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Abstract

Although tamoxifen is the most common and effective therapy for treatment of estrogen receptor-α (ER-α) breast cancer patients, resistance of endocrine therapy occurs, either de novo or acquired during therapy. Here, we investigated the clinical value of epidermal growth factor receptor (EGFR) in tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors, neratinib and gefitinib, on TamR breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker proteins, including N-cadherin (N-cad), fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of tamoxifen-treated breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors, neratinib and gefitinib, respectively. Interestingly, neratinib induced apoptotic cell death of TamR but not gefitinib. Cleaved PARP-1 expression was also increased by neratinib treatment in TamR cells. Therefore, we suggest that neratinib may be a potential therapeutic drug for treating TamR breast cancer.
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September-2015
Volume 34 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kim S, Lee J, Oh SJ, Nam SJ and Lee JE: Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells. Oncol Rep 34: 1613-1619, 2015
APA
Kim, S., Lee, J., Oh, S.J., Nam, S.J., & Lee, J.E. (2015). Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells. Oncology Reports, 34, 1613-1619. https://doi.org/10.3892/or.2015.4116
MLA
Kim, S., Lee, J., Oh, S. J., Nam, S. J., Lee, J. E."Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells". Oncology Reports 34.3 (2015): 1613-1619.
Chicago
Kim, S., Lee, J., Oh, S. J., Nam, S. J., Lee, J. E."Differential effect of EGFR inhibitors on tamoxifen-resistant breast cancer cells". Oncology Reports 34, no. 3 (2015): 1613-1619. https://doi.org/10.3892/or.2015.4116