Open Access

The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol

  • Authors:
    • José A. López-Méndez
    • José L. Ventura-Gallegos
    • Ignacio Camacho-Arroyo
    • Marcela Lizano
    • Alberto J. Cabrera-Quintero
    • Sandra L. Romero-Córdoba
    • Mariano Martínez-Vázquez
    • Nadia J. Jacobo-Herrera
    • Alfonso León-Del-Río
    • Adrian A. Paredes-Villa
    • Alejandro Zentella-Dehesa
  • View Affiliations

  • Published online on: November 15, 2023     https://doi.org/10.3892/ol.2023.14152
  • Article Number: 19
  • Copyright: © López-Méndez et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer expressing the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor‑2 (HER2) is known as triple‑positive (TPBC). TPBC represents 9‑11% of breast cancer cases worldwide and is a heterogeneous subtype. Notably, TPBC presents a therapeutic challenge due to the crosstalk between the hormonal (ER and PR) and HER2 pathways. Patients with TPBC are treated with trastuzumab (TTZ); however, several patients treated with TTZ tend to relapse. The present study aimed to investigate the effect of the PR on inhibitory effect of TTZ on cell viability. BT474 cells (a model of TPBC) and BT474 PR‑silenced cells were treated with either TTZ, progesterone (Pg), the PR antagonist mifepristone (RU486) or estradiol (E2) alone or in combination for 144 h (6 days). Cell viability assays and western blotting were subsequently performed. The results showed that Pg and E2 interfered with the inhibitory effect of TTZ on cell viability and this effect was potentiated when both hormones were combined. Pg was revealed to act through the PR, mainly activating the PR isoform B (PR‑B) and inducing the protein expression levels of CDK4 and cyclin D1; however, it did not reactivate the HER2/Akt pathway. By contrast, E2 was able to increase PR isoform A (PR‑A) expression, which was inhibited by Pg. Notably, in most of the experiments, RU486 did not antagonize the effects of Pg. In conclusion, Pg and E2 may interfere with the inhibitory effect of TTZ on cell viability through PR‑B activation and PR‑A inactivation.
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Spandidos Publications style
López-Méndez JA, Ventura-Gallegos JL, Camacho-Arroyo I, Lizano M, Cabrera-Quintero AJ, Romero-Córdoba SL, Martínez-Vázquez M, Jacobo-Herrera NJ, León-Del-Río A, Paredes-Villa AA, Paredes-Villa AA, et al: The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol. Oncol Lett 27: 19, 2024
APA
López-Méndez, J.A., Ventura-Gallegos, J.L., Camacho-Arroyo, I., Lizano, M., Cabrera-Quintero, A.J., Romero-Córdoba, S.L. ... Zentella-Dehesa, A. (2024). The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol. Oncology Letters, 27, 19. https://doi.org/10.3892/ol.2023.14152
MLA
López-Méndez, J. A., Ventura-Gallegos, J. L., Camacho-Arroyo, I., Lizano, M., Cabrera-Quintero, A. J., Romero-Córdoba, S. L., Martínez-Vázquez, M., Jacobo-Herrera, N. J., León-Del-Río, A., Paredes-Villa, A. A., Zentella-Dehesa, A."The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol". Oncology Letters 27.1 (2024): 19.
Chicago
López-Méndez, J. A., Ventura-Gallegos, J. L., Camacho-Arroyo, I., Lizano, M., Cabrera-Quintero, A. J., Romero-Córdoba, S. L., Martínez-Vázquez, M., Jacobo-Herrera, N. J., León-Del-Río, A., Paredes-Villa, A. A., Zentella-Dehesa, A."The inhibitory effect of trastuzumab on BT474 triple‑positive breast cancer cell viability is reversed by the combination of progesterone and estradiol". Oncology Letters 27, no. 1 (2024): 19. https://doi.org/10.3892/ol.2023.14152