Sorafenib and nilotinib resensitize tamoxifen resistant breast cancer cells to tamoxifen treatment via estrogen receptor α

  • Authors:
    • Astrid M. Pedersen
    • Susan Thrane
    • Anne E. Lykkesfeldt
    • Christina W. Yde
  • View Affiliations

  • Published online on: August 22, 2014     https://doi.org/10.3892/ijo.2014.2619
  • Pages: 2167-2175
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Abstract

Tamoxifen‑resistant breast cancer is a major clinical problem and new treatment strategies are highly warranted. In this study, the multitargeting kinase inhibitors sorafenib and nilotinib were investigated as potential new treatment options for tamoxifen‑resistant breast cancer. The two compounds inhibited cell growth, reduced expression of total estrogen receptor α (ER), Ser118-phosphorylated ER, FOXA1 and AIB1 and resensitized tamoxifen‑resistant cells to tamoxifen. The ER downmodulator fulvestrant exerted strong growth inhibition of tamoxifen‑resistant cells and addition of sorafenib and nilotinib could not further suppress growth, showing that sorafenib and nilotinib exerted growth inhibition via ER. In support of this, estradiol prevented sorafenib and nilotinib mediated growth inhibition. These results demonstrate that sorafenib and nilotinib act via ER and ER-associated proteins, indicating that these kinase inhibitors in combination with tamoxifen may be potential new treatments for tamoxifen‑resistant breast cancer.
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November-2014
Volume 45 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Pedersen AM, Thrane S, Lykkesfeldt AE and Yde CW: Sorafenib and nilotinib resensitize tamoxifen resistant breast cancer cells to tamoxifen treatment via estrogen receptor α. Int J Oncol 45: 2167-2175, 2014
APA
Pedersen, A.M., Thrane, S., Lykkesfeldt, A.E., & Yde, C.W. (2014). Sorafenib and nilotinib resensitize tamoxifen resistant breast cancer cells to tamoxifen treatment via estrogen receptor α. International Journal of Oncology, 45, 2167-2175. https://doi.org/10.3892/ijo.2014.2619
MLA
Pedersen, A. M., Thrane, S., Lykkesfeldt, A. E., Yde, C. W."Sorafenib and nilotinib resensitize tamoxifen resistant breast cancer cells to tamoxifen treatment via estrogen receptor α". International Journal of Oncology 45.5 (2014): 2167-2175.
Chicago
Pedersen, A. M., Thrane, S., Lykkesfeldt, A. E., Yde, C. W."Sorafenib and nilotinib resensitize tamoxifen resistant breast cancer cells to tamoxifen treatment via estrogen receptor α". International Journal of Oncology 45, no. 5 (2014): 2167-2175. https://doi.org/10.3892/ijo.2014.2619