• experimental
  
• epidemiological
  

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Medical/biological Study (experimental study)

Signal transduction of the melatonin receptor MT1 is disrupted in breast cancer cells by electromagnetic fields. med./biol.

PubMed Entry

Journal web site

Aim of study (according to author)
To study the effects of electromagnetic fields on the anti-proliferative effect of melatonin in breast cancer cell lines (melatonin suppresses the cell proliferation of breast cancer cells) expressing different amounts of the melatonin receptor (MT1).
In order to elucidate the underlying mechanism of this action, the regulation of transcription of the breast cancer susceptibility gene BRCA-1 and the expression of a number of other estrogen-regulated genes were analyzed in the presence of melatonin, either in sham exposed cells or in cells exposed to 1.2 µT of a 50 Hz electromagnetic field.
Background/further details:
Activation of melatonin receptor (MT1) by melatonin leads during the further signal transduction to diminished phosphorylation of the cAMP-responsive element binding protein. Additionally, the effect of melatonin on breast cancer cells depends on the presence of estrogen receptors because growth of estrogen receptor-negative breast cancer cells is not inhibited by melatonin. In contrast, the growth of estrogen-receptor positive breast cancer cells is inhibited by melatonin and concern has been raised that power line frequency and microwave electromagnetic fields could reduce the efficiency of melatonin on breast cancer cells.
Cell cultures were stimulated by estradiol and additionly treated with melatonin.

Endpoint

• cell function: signal transduction of the melatonin receptor MT1 in breast cancer cells

Exposure
General category: magnetic field, 50/60 Hz (AC)

Field characteristics	Parameters
50 Hz exposure duration: continuous for 48 hr	magnetic flux density: 1.2 µT

Exposed system:
intact cell/cell culture (in vitro)
MCF-7 (breast cancer cell line, parental cells and cells transfected with the MT1 gene (for the membrane-bound melatonin receptor))

Methods
Endpoint/Measurement parameters/Methodology

• molecular biosynthesis: expression of four estrogen-responsive genes (BRCA-1, p53, p21^WAF, and c-myc; RT-PCR and densitometric evaluation)
• cell function: binding of cAMP response element-binding protein to a promotor sequence of BRCA-1 gene (electrophoretic mobility shift assay)
• cell viability/cell division/proliferation: cell proliferation (AlamarBlue stain)

Main outcome of study (according to author)
In sham exposed cells, binding of cAMP response element-binding protein to the promoter of BRCA-1 gene was increased by estradiol and subsequently diminished by treatment with melatonin. In cells exposed to the 1.2 µT electromagnetic field binding of cAMP response element-binding protein was almost completely omitted.
Gene expression of the four estrogen-responsive genes was increased by estradiol stimulation and subsequently decreased by melatonin treatment in both cell lines, except for p53 expression in the transfected cell line, thereby proving the antiestrogenic effect of melatonin (i.e. attenuation of cell proliferation in estradiol stimulated breast cancer cells) at molecular level. In contrast, in breast cancer cells transfected with MT1 exposed to 1.2 µT of the 50 Hz electromagnetic field, the expression of p53 and c-myc increased significantly after melatonin treatment but for p21^WAF the increase was not significant.
These data prove the negative effect of electromagnetic fields on the antiestrogenic effect of melatonin in breast cancer cells (i.e. electromagnetic fields attenuate the growth inhibitory effect of melatonin in estradiol stimulated breast cancer cells). The comparison of the two cell lines differing strongly in the expression of MT1, revealed that the attenuation of these effects of estradiol by melatonin clearly depends on the expression of MT1.

(Study character: medical/biological study, experimental study, full/main study)

Study funded by

• Bundesministerium für Umwelt, Naturschutz und Reaktorsicherheit (Federal Ministry of the Environment, Nature Conservation, and Nuclear Safety), Germany

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