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Breast Cancer Research and Treatment

, Volume 115, Issue 1, pp 13–27 | Cite as

Role of melatonin in the epigenetic regulation of breast cancer

  • Ahmet KorkmazEmail author
  • Emilio J. Sanchez-Barcelo
  • Dun-Xian Tan
  • Russel J. Reiter
Review

Abstract

The oncostatic properties of melatonin as they directly or indirectly involve epigenetic mechanisms of cancer are reviewed with a special focus on breast cancer. Five lines of evidence suggest that melatonin works via epigenetic processes: (1) melatonin influences transcriptional activity of nuclear receptors (ERα, GR and RAR) involved in the regulation of breast cancer cell growth; (2) melatonin down-regulates the expression of genes responsible for the local synthesis or activation of estrogens including aromatase, an effect which may be mediated by methylation of the CYP19 gene or deacetylation of CYP19 histones; (3) melatonin inhibits telomerase activity and expression induced by either natural estrogens or xenoestrogens; (4) melatonin modulates the cell cycle through the inhibition of cyclin D1 expression; (5) melatonin influences circadian rhythm disturbances dependent on alterations of the light/dark cycle (i.e., light at night) with the subsequent deregulation of PER2 which acts as a tumor suppressor gene.

Keywords

Melatonin Breast cancer Epigenetic mechanisms Nuclear receptors Aromatase Telomerase Cell cycle Light at night Clock genes 

Notes

Acknowledgements

This work is supported in part by a grant from the Spanish Ministry of Education and Science (SAF2007-62762).

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Ahmet Korkmaz
    • 1
    • 2
    Email author
  • Emilio J. Sanchez-Barcelo
    • 3
  • Dun-Xian Tan
    • 2
  • Russel J. Reiter
    • 2
  1. 1.Department of Physiology, School of MedicineGulhane Military Medical AcademyAnkaraTurkey
  2. 2.Department of Cellular and Structural BiologyThe University of Texas Health Science Center at San AntonioSan Antonio78229USA
  3. 3.Department of Physiology and Pharmacology, School of MedicineUniversity of CantabriaSantanderSpain

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