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Biochemistry (Moscow)

, Volume 72, Issue 3, pp 320–327 | Cite as

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

  • Yu. S. Lobanova
  • A. M. Scherbakov
  • V. A. Shatskaya
  • M. A. Krasil’nikovEmail author
Article

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.

Key words

breast cancer apoptosis estrogens NF-κB phosphatidylinositol-3 kinase 

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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Copyright information

© Pleiades Publishing, Ltd. 2007

Authors and Affiliations

  • Yu. S. Lobanova
    • 1
  • A. M. Scherbakov
    • 2
  • V. A. Shatskaya
    • 1
  • M. A. Krasil’nikov
    • 1
    Email author
  1. 1.Institute of Carcinogenesis, Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia
  2. 2.Institute of Clinical Oncology, Blokhin Cancer Research CenterRussian Academy of Medical SciencesMoscowRussia

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