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Melatonin receptors, melatonin metabolizing enzymes and cyclin D1 in human breast cancer

Olga Rögelsperger1, Katrin Wlcek, Cem Ekmekcioglu

  • 1Department of Pathophysiology, Center for Pathophysiology and Allergy Research, Medical University of Vienna,Vienna, Austria.

Journal of Receptor and Signal Transduction Research
|March 10, 2011
PubMed
Abstract

Insights

Melatonin may inhibit breast cancer growth by affecting cell cycle regulators. Low expression of melatonin-metabolizing enzymes (CYP1A1/1A2) in tumors suggests melatonin

Area of Science:

  • Oncology
  • Endocrinology
  • Molecular Biology

Background:

  • Melatonin suppresses breast cancer cell proliferation by inhibiting estrogen-induced cyclin D1 via the MT1 receptor.
  • Melatonin also stimulates estrogen sulfotransferase (SULT1E1) expression.
  • Melatonin metabolism by CYP1A1/1A2 and SULT1A1/1A3 can decrease its concentration, potentially reducing its anti-cancer effects.

Purpose of the Study:

  • To investigate the expression of melatonin receptor (MT1), cyclin D1, and melatonin-metabolizing enzymes (CYP1A1/1A2, SULT1A1/1A3/1E1) in breast cancer specimens.
  • To determine the relationship between these factors and breast cancer characteristics.

Main Methods:

  • Immunohistochemical (IHC) analysis of MT1 and cyclin D1 in 33 breast cancer patients.
  • Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) to assess mRNA expression of CYP1A1/1A2, SULT1A1/1A3/1E1, and cyclin D1 in cancer and adjacent non-cancer tissues from 10 patients.

Main Results:

  • CYP1A1 mRNA was detected in limited cancer and non-cancer samples; CYP1A2 mRNA was below detection limits.
  • SULT1A1 was observed in few samples, while SULT1A3 showed high levels in all samples.
  • Cyclin D1 mRNA and IHC staining were present in most samples, with IHC staining correlating positively with estrogen receptor positivity.

Conclusions:

  • Low or absent expression of CYP1A1/CYP1A2 in breast cancer suggests a potential role for melatonin in cell cycle arrest.
  • The findings support the oncostatic role of melatonin in breast cancer, potentially independent of its major metabolic pathways.

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