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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
10:36

Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer

Published on: March 17, 2016

JNK pathway regulates estradiol-induced apoptosis in hormone-dependent human breast cancer cells

Nedret Altiok1, Meral Koyuturk, Soner Altiok

  • 1Department of Pharmacology and Institute of Medical Sciences, Istanbul Science University Faculty of Medicine, Büyükdere Cad. No: 120, 34394, Esentepe-Istanbul, Turkey. naltiok@superonline.com

Breast Cancer Research and Treatment
|December 26, 2006
PubMed

Insights

High doses of estrogen can trigger apoptosis and inhibit growth in ER-positive breast cancer cells by activating the c-jun NH2-terminal kinase (JNK) pathway. This suggests JNK activation as a potential therapeutic strategy for breast cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Estrogen typically promotes breast cancer development.
  • Paradoxically, high estrogen doses can cause hormone-dependent breast cancer regression in postmenopausal women.
  • The underlying mechanism for estrogen-induced tumor regression remains unclear.

Purpose of the Study:

  • To investigate the mechanism by which high concentrations of 17-beta-estradiol (estradiol) induce apoptosis in estrogen receptor (ER)-positive breast cancer cells.
  • To determine the role of the c-jun NH2-terminal kinase (JNK) signaling pathway in mediating estradiol's anti-cancer effects.

Main Methods:

  • Treatment of ER-positive (MCF-7) and ER-negative (MDA-MB 231) breast cancer cell lines with high concentrations of estradiol under low growth-stimulated conditions.
  • Assessment of apoptosis induction and c-jun phosphorylation.
  • Inhibition of the JNK signaling pathway using SP600125 to evaluate its impact on estradiol's effects.

Main Results:

  • High estradiol concentrations induced apoptosis and increased c-jun phosphorylation in MCF-7 cells, but not in MDA-MB 231 cells, indicating an ER-mediated process.
  • Disruption of the JNK signaling pathway with SP600125 completely blocked estradiol's ability to inhibit MCF-7 cell growth and induce apoptosis.
  • These findings highlight the central role of JNK in mediating the anti-cancer effects of high-dose estradiol.

Conclusions:

  • High-dose estradiol induces apoptosis in ER-positive breast cancer cells via JNK activation under specific conditions.
  • Augmenting JNK activity presents a potential novel therapeutic strategy for breast cancer treatment.
  • These findings have implications for the pharmacological control of breast cancer in postmenopausal women using high-dose estrogen therapy.

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