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Article

Melatonin modulates aromatase activity and expression in endothelial cells

  • Authors:
    • Virginia Alvarez-García
    • Alicia González
    • Carlos Martínez-Campa
    • Carolina Alonso-González
    • Samuel Cos
  • View Affiliations / Copyright

    Affiliations: Department of Physiology and Pharmacology, School of Medicine, University of Cantabria, 39011 Santander, Spain
  • Pages: 2058-2064
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    Published online on: February 28, 2013
       https://doi.org/10.3892/or.2013.2314
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Abstract

Melatonin is known to suppress the development of endocrine-responsive breast cancers by interacting with the estrogen signaling pathways. Paracrine interactions between malignant epithelial cells and proximal stromal cells are responsible for local estrogen biosynthesis. In human breast cancer cells and peritumoral adipose tissue, melatonin downregulates aromatase, which transforms androgens into estrogens. The presence of aromatase on endothelial cells indicates that endothelial cells may contribute to tumor growth by producing estrogens. Since human umbilical vein endothelial cells (HUVECs) express both aromatase and melatonin receptors, the aim of the present study was to evaluate the ability of melatonin to regulate the activity and expression of aromatase on endothelial cells, thus, modulating local estrogen biosynthesis. In the present study, we demonstrated that melatonin inhibits the growth of HUVECs and reduces the local biosynthesis of estrogens through the downregulation of aromatase. These results are supported by three lines of evidence. Firstly, 1 mM of melatonin counteracted the testosterone-induced cell proliferation of HUVECs, which is dependent on the local biosynthesis of estrogens from testosterone by the aromatase activity of the cells. Secondly, we found that 1 mM of melatonin reduced the aromatase activity of HUVECs. Finally, by real‑time RT-PCR, we demonstrated that melatonin significantly downregulated the expression of aromatase as well as its endothelial-specific aromatase promoter region I.7. We conclude that melatonin inhibits aromatase activity and expression in HUVECs by regulating gene expression of specific aromatase promoter regions, thereby reducing the local production of estrogens.
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Copy and paste a formatted citation
Spandidos Publications style
Alvarez-García V, González A, Martínez-Campa C, Alonso-González C and Cos S: Melatonin modulates aromatase activity and expression in endothelial cells. Oncol Rep 29: 2058-2064, 2013.
APA
Alvarez-García, V., González, A., Martínez-Campa, C., Alonso-González, C., & Cos, S. (2013). Melatonin modulates aromatase activity and expression in endothelial cells. Oncology Reports, 29, 2058-2064. https://doi.org/10.3892/or.2013.2314
MLA
Alvarez-García, V., González, A., Martínez-Campa, C., Alonso-González, C., Cos, S."Melatonin modulates aromatase activity and expression in endothelial cells". Oncology Reports 29.5 (2013): 2058-2064.
Chicago
Alvarez-García, V., González, A., Martínez-Campa, C., Alonso-González, C., Cos, S."Melatonin modulates aromatase activity and expression in endothelial cells". Oncology Reports 29, no. 5 (2013): 2058-2064. https://doi.org/10.3892/or.2013.2314
Copy and paste a formatted citation
x
Spandidos Publications style
Alvarez-García V, González A, Martínez-Campa C, Alonso-González C and Cos S: Melatonin modulates aromatase activity and expression in endothelial cells. Oncol Rep 29: 2058-2064, 2013.
APA
Alvarez-García, V., González, A., Martínez-Campa, C., Alonso-González, C., & Cos, S. (2013). Melatonin modulates aromatase activity and expression in endothelial cells. Oncology Reports, 29, 2058-2064. https://doi.org/10.3892/or.2013.2314
MLA
Alvarez-García, V., González, A., Martínez-Campa, C., Alonso-González, C., Cos, S."Melatonin modulates aromatase activity and expression in endothelial cells". Oncology Reports 29.5 (2013): 2058-2064.
Chicago
Alvarez-García, V., González, A., Martínez-Campa, C., Alonso-González, C., Cos, S."Melatonin modulates aromatase activity and expression in endothelial cells". Oncology Reports 29, no. 5 (2013): 2058-2064. https://doi.org/10.3892/or.2013.2314
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