Open Access

A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells

  • Authors:
    • Ann‑Katrin Sommer
    • Adam Hermawan
    • Bojan Ljepoja
    • Thomas Fröhlich
    • Georg J. Arnold
    • Ernst Wagner
    • Andreas Roidl
  • View Affiliations

  • Published online on: July 18, 2018     https://doi.org/10.3892/ijmm.2018.3781
  • Pages: 1987-1997
  • Copyright: © Sommer et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer exhibits the highest incidence of all cancer types and is the 2nd leading cause of cancer mortality in women. Up to 82% of breast cancer patients receive a chemotherapy‑containing treatment regimen. However, numerous breast tumors recur within 10 years following an initial response and are frequently resistant to previous therapeutic agents. Thus, to analyze the crucial factors, and whether the development of resistance in tumor cells follows certain patterns, is of great importance. In the present study, the clinical treatment schedule of the frequently used chemotherapeutic drug doxorubicin was applied in an in vitro model, the Molecular Evolution Assay (MEA), leading to resistance formation. By investigating the alterations in protein expression in MCF‑7 breast cancer cells with three biological replicates, it was observed that the development of resistance to doxorubicin is a multi‑directed process. The number and composition of the differentially expressed proteins varied, in addition to the pathways involved in chemoresistance, leading to only a small number of proteins and pathways being commonly regulated in all the MEAs. The proteins 60S ribosomal export protein NMD3 and 4F2 cell‑surface antigen heavy chain (SLC3A2) were identified to be the most promising differentially expressed targets; the gene ontology term ‘apoptotic signaling pathway’ was reduced and ‘cell redox homeostasis’ was upregulated. Based on the present findings in vitro, it may be hypothesized that the development of resistance in patients is an even more complex process, emphasizing the need for further investigations of resistance development in the clinic to eventually improve patient outcomes.
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October-2018
Volume 42 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Sommer AK, Hermawan A, Ljepoja B, Fröhlich T, Arnold GJ, Wagner E and Roidl A: A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells. Int J Mol Med 42: 1987-1997, 2018
APA
Sommer, A., Hermawan, A., Ljepoja, B., Fröhlich, T., Arnold, G.J., Wagner, E., & Roidl, A. (2018). A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells. International Journal of Molecular Medicine, 42, 1987-1997. https://doi.org/10.3892/ijmm.2018.3781
MLA
Sommer, A., Hermawan, A., Ljepoja, B., Fröhlich, T., Arnold, G. J., Wagner, E., Roidl, A."A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells". International Journal of Molecular Medicine 42.4 (2018): 1987-1997.
Chicago
Sommer, A., Hermawan, A., Ljepoja, B., Fröhlich, T., Arnold, G. J., Wagner, E., Roidl, A."A proteomic analysis of chemoresistance development via sequential treatment with doxorubicin reveals novel players in MCF‑7 breast cancer cells". International Journal of Molecular Medicine 42, no. 4 (2018): 1987-1997. https://doi.org/10.3892/ijmm.2018.3781