Signal transduction of the melatonin receptor mt1 is disrupted in breast cancer cells by electromagnetic fields

Wiley InterScience :: JOURNALS :: Bioelectromagnetics http://www3.interscience.wiley.com/journal/122668648/abstract My Profile
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Regular Article
Signal transduction of the melatonin receptor MT1 is disrupted in breast cancer cells by
electromagnetic fields
, Volker Hanf , Günter Emons , Carsten Gründker 1Department of Gynecology and Obstetrics, University of Göttingen, Göttingen, Germany
2Department of Nephrology, University of Göttingen, Göttingen, Germany
3Department of Gynecology and Obstetrics, Klinikum Fürth, Fürth, Germany
email: Rainer Girgert (rainer.girgert@med.uni-goettingen.de)
*Correspondence to Rainer Girgert, Department of Nephrology, University of Göttingen, Robert-Koch-Strasse 40, D-37075 Göttingen,Germany.
Funded by:
German Federal Ministry for Environment, Nature Conservation and Nuclear Safety; Grant Number: StSch4219, StSch4461 KEYWORDS
breast cancer • electromagnetic fields • gene expression • melatonin ABSTRACT
The growth of estrogen-receptor positive breast cancer cells is inhibited by the pineal gland hormone, melatonin. Concern has beenraised that power-line frequency and microwave electromagnetic fields (EMFs) could reduce the efficiency of melatonin on breast cancercells. In this study we investigated the impact of EMFs on the signal transduction of the high-affinity receptor MT1 in parental MCF-7cells and MCF-7 cells transfected with the MT1 gene. The binding of the cAMP-responsive element binding (CREB) protein to apromoter sequence of BRCA-1 after stimulation with melatonin was analyzed by a gel-shift assay and the expression of four estrogen-responsive genes was measured in sham-exposed breast cancer cells and cells exposed to a sinusoidal 50 Hz EMF of 1.2 µT for 48 h.
In sham-exposed cells, binding of CREB to the promoter of BRCA-1 was increased by estradiol and subsequently diminished bytreatment with melatonin. In cells exposed to 1.2 µT, 50 Hz EMF, binding of CREB was almost completely omitted. Expression of BRCA-1, p53, p21WAF, and c-myc was increased by estradiol stimulation and subsequently decreased by melatonin treatment in bothcell lines, except for p53 expression in the transfected cell line, thereby proving the antiestrogenic effect of melatonin at molecular level.
In contrast, in breast cancer cells transfected with MT1 exposed to 1.2 µT of the 50 Hz EMF, the expression of p53 and c-myc increased significantly after melatonin treatment but for p21WAF the increase was not significant. These results convincingly prove the negativeeffect of EMF on the antiestrogenic effect of melatonin in breast cancer cells. Bioelectromagnetics, 2009. 2009 Wiley-Liss, Inc.
Received: 23 January 2009; Revised: 30 July 2009 DIGITAL OBJECT IDENTIFIER (DOI)
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