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Mechanism of estrogen-induced apoptosis in breast cancer cells: Role of the NF-κB signaling pathway

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Abstract

The ability of sex steroid hormones to up-regulate the apoptotic signaling proteins is well documented; however, the apoptotic potential of sex hormones is not remarkable and fully compensated by their growth stimulatory action to target cells. In the present study using the long-term cultivation of estrogen-dependent MCF-7 breast cancer cells in steroid-free medium, we have established a cell subline, designed as MCF-7/LS, which was characterized by the resistance to growth stimulatory estradiol action and hypersensitivity to estrogen-induced apoptosis. We have demonstrated that estrogen treatment of the cells does not influence on the level of TNF-R1 or Fas, but dramatically decreases the transcriptional activity of NF-κB. Importantly, the MCF-7/LS cells, which are insensitive to growth stimulatory estrogen action, retain the ability to decrease in the NF-κB activity in response to estrogen stimulus. Furthermore, the significant increase in the basal (in the absence of ligand) estrogen receptor (ER)-dependent transcriptional activity in the MCF-7/LS cells was revealed and reciprocal transcriptional antagonism between ER and NF-κB was demonstrated. Finally, we proved the possible involvement of phosphatidylinositol-3 kinase (PI3K) in the ligand-independent ER activation. In general, the results presented suggest that long-term growth of MCF-7 breast cancer cells in steroid-free medium is accompanied with the increase in the basal ER-dependent transcriptional activity as well as the maintenance of the negative regulatory loop ER-NF-κB. The latter may be considered as one of the factors resulting in a disbalance between pro-and anti-apoptotic pathways and enhancement in estrogen apoptotic action in the cells.

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Abbreviations

ER:

estrogen receptor

ERE:

estrogen responsive element

MTT:

3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

PI:

propidium iodide

PI3K:

phosphatidylinositol-3 kinase

PTEN:

phosphatase dephosphorylating 3-OH-phosphoinositides

TNF-α:

tumor necrosis factor α

TNF-R1:

type I tumor necrosis factor receptor

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Authors and Affiliations

  1. Institute of Carcinogenesis, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478, Moscow, Russia

    Yu. S. Lobanova, V. A. Shatskaya & M. A. Krasil’nikov

  2. Institute of Clinical Oncology, Blokhin Cancer Research Center, Russian Academy of Medical Sciences, Kashirskoe Shosse 24, 115478, Moscow, Russia

    A. M. Scherbakov

Authors
  1. Yu. S. Lobanova
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  2. A. M. Scherbakov
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  3. V. A. Shatskaya
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  4. M. A. Krasil’nikov
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Correspondence to M. A. Krasil’nikov.

Additional information

Original Russian Text © Yu. S. Lobanova, A. M. Scherbakov, V. A. Shatskaya, M. A. Krasil’nikov, 2007, published in Biokhimiya, 2007, Vol. 72, No. 3, pp. 392–401.

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Lobanova, Y.S., Scherbakov, A.M., Shatskaya, V.A. et al. Mechanism of estrogen-induced apoptosis in breast cancer cells: Role of the NF-κB signaling pathway. Biochemistry Moscow 72, 320–327 (2007). https://doi.org/10.1134/S0006297907030108

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  • DOI: https://doi.org/10.1134/S0006297907030108

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