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Modulation of the Estrogen Response Pathway in Human Breast Cancer Cells by Melatonin

  • Chapter
The Pineal Gland and Cancer

Abstract

The pineal hormone melatonin has been shown to exert an inhibitory influence only on estrogen receptor (ER)-positive human breast tumor cell lines and to modulate ER expression, suggesting that melatonin’s actions may be linked to the cell’s estrogen response pathway. Two distinct melatonin receptors have recently been identified, a membrane-bound G protein-coupled receptor (Mella) and a nuclear orphan receptor (RZR/RORα) belonging to the retinoic acid receptor class. Melatonin’s antitumorigenic effects in MCF-7 cells have been shown to be mediated via the Mella receptor and appear to be serum-dependent. We investigated whether melatonin, alone or in conjunction with serum factors such as EGF and insulin, can modulate ER activity by affecting ER phosphorylation and transactivation. We found that melatonin alone decreased ER phosphorylation but did not transactivate the ER. However, a combined treatment with melatonin followed by either EGF or insulin stimulated mitogen-activated protein kinase (MAPK) activity and induced ER phosphorylation, leading to transactivation of the human ER. Taken together, these findings suggest the possibility of cross talk between the melatonin receptor pathway and the tyrosine kinase receptor pathways.

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Authors
  1. Steven M. Hill
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  2. Todd Kiefer
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  3. Stephenie Teplitzky
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  4. Louaine L. Spriggs
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  5. Prahlad Ram
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Editors and Affiliations

  1. Centre for Research in Medical and Natural Sciences, University of Tübingen, Ob dem Himmelreich 7, Tübingen, 72074, Germany

    Christian Bartsch  & Hella Bartsch  & 

  2. Laboratory of Experimental Neuroendocrinology/Oncology, Bassett Research Institute, One Atwell Road, Cooperstown, NY, 13326, USA

    David E. Blask Ph.D.,M.D. (Senior Research Scientist) (Senior Research Scientist)

  3. Department of Physiology Faculty of Medicine, University of Buenos Aires, Paraguay 2155, Buenos Aires, 121, Argentina

    Daniel P. Cardinali M.D.,Ph.D.

  4. WJB Dorn VA Medical Center, University of South Carolina, 6439 Garners Ferry Road, Columbia, SC, 29209, USA

    William J. M. Hrushesky M.D. (Director of Research (151) (Director of Research (151)

  5. Institute of Physiological Chemistry, University of Tübingen, Hoppe-Seyler-Str. 4, Tübingen, 72076, Germany

    Dieter Mecke (Director) (Director)

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Hill, S.M., Kiefer, T., Teplitzky, S., Spriggs, L.L., Ram, P. (2001). Modulation of the Estrogen Response Pathway in Human Breast Cancer Cells by Melatonin. In: Bartsch, C., Bartsch, H., Blask, D.E., Cardinali, D.P., Hrushesky, W.J.M., Mecke, D. (eds) The Pineal Gland and Cancer. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59512-7_16

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  • DOI: https://doi.org/10.1007/978-3-642-59512-7_16

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