Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells

  • Authors:
    • Elizabeth E. Sweeney
    • Ping Fan
    • V. Craig Jordan
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  • Published online on: March 6, 2014     https://doi.org/10.3892/ijo.2014.2329
  • Pages: 1529-1538
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Abstract

Models of long-term estrogen-deprived breast cancer cells are utilized in the laboratory to mimic clinical aromatase inhibitor-resistant breast cancer and serve as a tool to discover new therapeutic strategies. The MCF-7:5C and MCF-7:2A subclones were generated through long-term estrogen deprivation of estrogen receptor (ER)-positive MCF-7 cells, and represent anti-hormone‑resistant breast cancer. MCF-7:5C cells paradoxically undergo estrogen-induced apoptosis within seven days of estrogen (estradiol, E2) treatment; MCF-7:2A cells also experience E2-induced apoptosis but evade dramatic cell death until approximately 14 days of treatment. To discover and define the mechanisms by which MCF-7:2A cells survive two weeks of E2 treatment, systematic experiments were performed in this study. The data suggest that MCF-7:2A cells employ stronger antioxidant defense mechanisms than do MCF-7:5C cells, and that oxidative stress is ultimately required for MCF-7:2A cells to die in response to E2 treatment. Tumor necrosis factor (TNF) family member activation is also essential for E2-induced apoptosis to occur in MCF-7:2A cells; upregulation of TNFα occurs simultaneously with oxidative stress activation. Although the unfolded protein response (UPR) signaling pattern is similar to that in MCF-7:5C cells, it is not sufficient to cause cell death in MCF-7:2A cells. Additionally, increased insulin-like growth factor receptor β (IGF-1Rβ) confers a mechanism of growth and anti-apoptotic advantage in MCF-7:2A cells.
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May-2014
Volume 44 Issue 5

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

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Spandidos Publications style
Sweeney EE, Fan P and Jordan VC: Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells. Int J Oncol 44: 1529-1538, 2014
APA
Sweeney, E.E., Fan, P., & Jordan, V.C. (2014). Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells. International Journal of Oncology, 44, 1529-1538. https://doi.org/10.3892/ijo.2014.2329
MLA
Sweeney, E. E., Fan, P., Jordan, V. C."Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells". International Journal of Oncology 44.5 (2014): 1529-1538.
Chicago
Sweeney, E. E., Fan, P., Jordan, V. C."Mechanisms underlying differential response to estrogen-induced apoptosis in long-term estrogen-deprived breast cancer cells". International Journal of Oncology 44, no. 5 (2014): 1529-1538. https://doi.org/10.3892/ijo.2014.2329