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

Abstract

The growth of estrogen-receptor positive breast cancer cells is inhibited by the pineal gland hormone, melatonin. Concern has been raised that power-line frequency and microwave electromagnetic fields (EMFs) could reduce the efficiency of melatonin on breast cancer cells. In this study we investigated the impact of EMFs on the signal transduction of the high-affinity receptor MT1 in parental MCF-7 cells and MCF-7 cells transfected with the MT1 gene. The binding of the cAMP-responsive element binding (CREB) protein to a promoter 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 microT for 48 h. In sham-exposed cells, binding of CREB to the promoter of BRCA-1 was increased by estradiol and subsequently diminished by treatment with melatonin. In cells exposed to 1.2 microT, 50 Hz EMF, binding of CREB was almost completely omitted. Expression of BRCA-1, p53, p21(WAF), and c-myc 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 at molecular level. In contrast, in breast cancer cells transfected with MT1 exposed to 1.2 microT of the 50 Hz EMF, the expression of p53 and c-myc increased significantly after melatonin treatment but for p21(WAF) the increase was not significant. These results convincingly prove the negative effect of EMF on the antiestrogenic effect of melatonin in breast cancer cells.

AI evidence extraction

Main findings

Cells were exposed to a sinusoidal 50 Hz EMF (1.2 microT) for 48 h. In sham-exposed cells, melatonin diminished estradiol-induced CREB binding to the BRCA-1 promoter, whereas in EMF-exposed cells CREB binding was almost completely omitted. In MT1-transfected cells exposed to EMF, p53 and c-myc expression increased significantly after melatonin treatment (p21(WAF) increase not significant), which the authors interpret as a negative effect of EMF on melatonin’s antiestrogenic action.

Outcomes measured

• MT1 receptor signal transduction
• CREB binding to BRCA-1 promoter (gel-shift assay)
• Expression of estrogen-responsive genes (BRCA-1, p53, p21(WAF), c-myc) after estradiol and melatonin treatment

Limitations

• In vitro cell culture study; findings may not generalize to humans
• Sample size and replication details not provided in abstract
• Only one ELF exposure condition reported (50 Hz, 1.2 microT, 48 h)

Suggested hubs

• occupational-exposure (0.35)
  Study uses power-line frequency (50 Hz) ELF exposure relevant to power/occupational contexts, though conducted in vitro.

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    "study_type": "in_vitro",
    "exposure": {
        "band": "ELF",
        "source": "power-line frequency",
        "frequency_mhz": null,
        "sar_wkg": null,
        "duration": "48 h"
    },
    "population": "Breast cancer cell lines (parental MCF-7 and MCF-7 cells transfected with MT1 gene)",
    "sample_size": null,
    "outcomes": [
        "MT1 receptor signal transduction",
        "CREB binding to BRCA-1 promoter (gel-shift assay)",
        "Expression of estrogen-responsive genes (BRCA-1, p53, p21(WAF), c-myc) after estradiol and melatonin treatment"
    ],
    "main_findings": "Cells were exposed to a sinusoidal 50 Hz EMF (1.2 microT) for 48 h. In sham-exposed cells, melatonin diminished estradiol-induced CREB binding to the BRCA-1 promoter, whereas in EMF-exposed cells CREB binding was almost completely omitted. In MT1-transfected cells exposed to EMF, p53 and c-myc expression increased significantly after melatonin treatment (p21(WAF) increase not significant), which the authors interpret as a negative effect of EMF on melatonin’s antiestrogenic action.",
    "effect_direction": "harm",
    "limitations": [
        "In vitro cell culture study; findings may not generalize to humans",
        "Sample size and replication details not provided in abstract",
        "Only one ELF exposure condition reported (50 Hz, 1.2 microT, 48 h)"
    ],
    "evidence_strength": "low",
    "confidence": 0.7800000000000000266453525910037569701671600341796875,
    "peer_reviewed_likely": "yes",
    "keywords": [
        "ELF EMF",
        "50 Hz",
        "1.2 microT",
        "melatonin",
        "MT1 receptor",
        "MCF-7",
        "breast cancer cells",
        "CREB",
        "BRCA-1",
        "estrogen-responsive genes",
        "p53",
        "c-myc",
        "p21(WAF)"
    ],
    "suggested_hubs": [
        {
            "slug": "occupational-exposure",
            "weight": 0.34999999999999997779553950749686919152736663818359375,
            "reason": "Study uses power-line frequency (50 Hz) ELF exposure relevant to power/occupational contexts, though conducted in vitro."
        }
    ]
}

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