Open Access

Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents

  • Authors:
    • Alexander M. Scherbakov
    • Danila V. Sorokin
    • Valeria E. Razuvaeva
    • Yuri Yu. Shchegolev
    • Olga E. Andreeva
    • Diana I. Salnikova
    • Timur I. Fetisov
    • Olga A. Vlasova
    • Kirill I. Kirsanov
    • Margarita V. Gudkova
    • Mikhail A. Krasil'nikov
  • View Affiliations

  • Published online on: January 19, 2024     https://doi.org/10.3892/br.2024.1727
  • Article Number: 42
  • Copyright : © Scherbakov et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Combining chemotherapy and hormone therapy is a prevalent approach in breast cancer treatment. While the cytotoxic impact of numerous chemotherapy drugs stems from DNA damage, the exact role of these DNA alterations in modulating estrogen receptor α (ERα) machinery remains elusive. The present study aimed to analyze the impact of DNA damage agents on ERα signaling in breast cancer cells and assess the signaling pathways mediating the influence of DNA damage drugs on the ERα machinery. Cell viability was assessed using the MTT method, while the expression of signaling proteins was analyzed by immunoblotting. ERα activity in the cells treated with various drugs (17β‑estradiol, tamoxifen, 5‑fluorouracil) was assessed through reporter gene assays. In vitro experiments were conducted on MCF7 breast cancer cells subjected to varying durations of 5‑fluorouracil (5‑FU) treatment. Two distinct cell responses to 5‑FU were identified based on the duration of the treatment. A singular dose of 5‑FU induces pronounced DNA fragmentation, temporally suppressing ERα signaling while concurrently activating AKT phosphorylation. This suppression reverses upon 5‑FU withdrawal, restoring normalcy within ten days. However, chronic 5‑FU treatment led to the emergence of 5‑FU‑resistant cells with irreversible alterations in ERα signaling, resulting in partial hormonal resistance. These changes mirror those observed in cells subjected to UV‑induced DNA damage, underscoring the pivotal role of DNA damage in shaping estrogen signaling alterations in breast cancer cells. In summary, the results of the present study suggested that the administration of DNA damage agents to cancer cells can trigger irreversible suppression of estrogen signaling, fostering the development of partial hormonal resistance. This outcome may ultimately impede the efficacy of combined or subsequent chemo‑ and hormone therapy strategies.
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March-2024
Volume 20 Issue 3

Print ISSN: 2049-9434
Online ISSN:2049-9442

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Spandidos Publications style
Scherbakov AM, Sorokin DV, Razuvaeva VE, Shchegolev YY, Andreeva OE, Salnikova DI, Fetisov TI, Vlasova OA, Kirsanov KI, Gudkova MV, Gudkova MV, et al: Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents. Biomed Rep 20: 42, 2024
APA
Scherbakov, A.M., Sorokin, D.V., Razuvaeva, V.E., Shchegolev, Y.Y., Andreeva, O.E., Salnikova, D.I. ... Krasil'nikov, M.A. (2024). Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents. Biomedical Reports, 20, 42. https://doi.org/10.3892/br.2024.1727
MLA
Scherbakov, A. M., Sorokin, D. V., Razuvaeva, V. E., Shchegolev, Y. Y., Andreeva, O. E., Salnikova, D. I., Fetisov, T. I., Vlasova, O. A., Kirsanov, K. I., Gudkova, M. V., Krasil'nikov, M. A."Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents". Biomedical Reports 20.3 (2024): 42.
Chicago
Scherbakov, A. M., Sorokin, D. V., Razuvaeva, V. E., Shchegolev, Y. Y., Andreeva, O. E., Salnikova, D. I., Fetisov, T. I., Vlasova, O. A., Kirsanov, K. I., Gudkova, M. V., Krasil'nikov, M. A."Irreversible inhibition of estrogen receptor α signaling and the emergence of hormonal resistance in MCF7 breast cancer cells induced by DNA damage agents". Biomedical Reports 20, no. 3 (2024): 42. https://doi.org/10.3892/br.2024.1727