Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells

  • Authors:
    • A. González
    • C. Martínez-Campa
    • M. D. Mediavilla
    • C. Alonso-González
    • S. Sánchez-Mateos
    • S. M. Hill
    • E. J. Sánchez-Barceló
    • S. Cos
  • View Affiliations

  • Published online on: April 1, 2007     https://doi.org/10.3892/or.17.4.947
  • Pages: 947-953
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Abstract

A major mechanism through which melatonin reduces the development of breast cancer is based on its anti-estrogenic actions by interfering at different levels with the estrogen-signalling pathways. Melatonin inhibits both aromatase activity and expression in vitro (MCF-7 cells) as well as in vivo, thus behaving as a selective estrogen enzyme modulator. The objective of this study was to study the effect of MT1 melatonin receptor overexpression in MCF-7 breast cancer cells on the aromatase-suppressive effects of melatonin. Transfection of the MT1 melatonin receptor in MCF-7 cells significantly decreased aromatase activity of the cells and MT1-transfected cells showed a level of aromatase activity that was 50% of vector-transfected MCF-7 cells. The proliferation of estrogen-sensitive MCF-7 cells in an estradiol-free media but in the presence of testosterone (an indirect measure of aromatase activity) was strongly inhibited by melatonin in those cells overexpressing the MT1 receptor. This inhibitory effect of melatonin on cell growth was higher on MT1 transfected cells than in vector transfected ones. In MT1-transfected cells, aromatase activity (measured by the tritiated water release assay) was inhibited by melatonin (20% at 1 nM; 40% at 10 µM concentrations). The same concentrations of melatonin did not significantly influence the aromatase activity of vector-transfected cells. MT1 melatonin receptor transfection also induced a significant 55% inhibition of aromatase steady-state mRNA expression in comparison to vector-transfected MCF-7 cells (p<0.001). In addition, in MT1-transfected cells melatonin treatment inhibited aromatase mRNA expression and 1 nM melatonin induced a higher and significant down-regulation of aromatase mRNA expression (p<0.05) than in vector-transfected cells. The findings presented herein point to the importance of MT1 melatonin receptor in mediating the oncostatic action of melatonin in MCF-7 human breast cancer cells and confirm MT1 melatonin receptor as a major mediator in the melatonin signalling pathway in breast cancer.

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April 2007
Volume 17 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
González A, Martínez-Campa C, Mediavilla MD, Alonso-González C, Sánchez-Mateos S, Hill SM, Sánchez-Barceló EJ and Cos S: Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells. Oncol Rep 17: 947-953, 2007
APA
González, A., Martínez-Campa, C., Mediavilla, M.D., Alonso-González, C., Sánchez-Mateos, S., Hill, S.M. ... Cos, S. (2007). Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells. Oncology Reports, 17, 947-953. https://doi.org/10.3892/or.17.4.947
MLA
González, A., Martínez-Campa, C., Mediavilla, M. D., Alonso-González, C., Sánchez-Mateos, S., Hill, S. M., Sánchez-Barceló, E. J., Cos, S."Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells". Oncology Reports 17.4 (2007): 947-953.
Chicago
González, A., Martínez-Campa, C., Mediavilla, M. D., Alonso-González, C., Sánchez-Mateos, S., Hill, S. M., Sánchez-Barceló, E. J., Cos, S."Effects of MT1 melatonin receptor overexpression on the aromatase-suppressive effect of melatonin in MCF-7 human breast cancer cells". Oncology Reports 17, no. 4 (2007): 947-953. https://doi.org/10.3892/or.17.4.947