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Systems Biology of Metabolic Regulation by Estrogen Receptor Signaling in Breast Cancer
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Promoting E2F1-mediated apoptosis in oestrogen receptor-α-negative breast cancer cells

María F Montenegro1, María Del Mar Collado-González, María Piedad Fernández-Pérez

  • 1Department of Biochemistry and Molecular Biology A, School of Biology, Regional Campus of International Excellence "Campus Mare Nostrum", University of Murcia, 30100 Espinardo, Murcia, Spain. fermontenegro@um.es.

BMC Cancer
|July 28, 2014
PubMed
Abstract

Insights

Tamoxifen resistance in ERα-negative breast cancer cells was investigated. A novel therapy combining 4-hydroxy-tamoxifen (4OHT) with TMCG/DIPY effectively targeted overexpressed E2F1, inducing cancer cell death.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Oestrogen receptor α (ERα) regulates E2F1, mediating tamoxifen resistance in ERα-positive breast cancer.
  • The role of ERα and E2F1 in tamoxifen resistance in ERα-negative breast cancer remains to be defined.

Purpose of the Study:

  • To investigate the roles of ERα and E2F1 in promoting 4-hydroxy-tamoxifen (4OHT) resistance in ERα-negative breast cancer cells.
  • To evaluate a novel therapeutic strategy combining 4OHT with dipyridamole (DIPY) and 3-O-(3,4,5-trimethoxybenzoyl)-(-)-catechin (TMCG).

Main Methods:

  • Utilized conventional techniques to assess 4OHT effects on ERα and E2F1 expression in MDA-MB-231 cells.
  • Examined the effects of 4OHT, DIPY, and TMCG individually and in combination using viability assays, Hoechst staining, MALDI-TOF mass spectroscopy, and confocal microscopy.

Main Results:

  • 4-hydroxy-tamoxifen (4OHT) up-regulated ERα in ERα-negative MDA-MB-231 cells, promoting E2F1-mediated cell growth.
  • E2F1 exhibits a dual role in cell growth and apoptosis.
  • The combination therapy of 4OHT with TMCG/DIPY enhanced toxicity in 4OHT-treated ERα-negative breast cancer cells.

Conclusions:

  • Therapeutic strategies targeting the epigenetic machinery, specifically modulating E2F1 methylation and stability, can induce E2F1-mediated cancer cell death.
  • The combination of TMCG/DIPY with 4OHT shows promise for treating ERα-negative breast cancer by exploiting overexpressed E2F1.

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