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.

Influence of a 50 Hz magnetic field and of all-trans‑retinol on the proliferation of human cancer cell lines

“…As a matter of fact, the in vitro response to ELF fields has been shown to be modulated by a variety of physical and/ or biological parameters that could potentiate or inhibit the cellular sensitivity to MF. These parameters include the field strength, the wave form, the exposure cycle and duration, the genetic characteristics of the cells (66), the presence of pharmacological drugs or endogenous hormones like melatonin (19,67) or the redox status of the system (68). Pirozzoli et al (69) reported a significant increase (10%; p≤0.05) in proliferation of the human neuroblastoma cell line LAN-5, after 7 days of continuous exposure to 50 Hz, 1 mT MF.…”

“…In order to identify and characterize the cellular processes involved in the potential proliferative effects of ELF MF, a number of studies have investigated the in vitro response to those fields when administered in combination with different chemical species including antioxidants like melatonin or tamoxifen (14)(15)(16)(17)(18)(19), or radical-inducing agents like menadione (20) and tumor promoters like DMBA (21).…”

Searching for the Perfect Wave: The Effect of Radiofrequency Electromagnetic Fields on Cells

“…However, it also acts as a natural free radical antioxidant scavenger. This would explain its beneficial effect in reducing EMF-induced damage in breast cancer model [83] and its neuroprotective rescue after RF oxidative stress induction in neuron primary culture [84]. Interestingly, melatonin has been reported to play a relevant role in regulation of human newborn protection in enhanced environmental oxidative stress (OS) present at time of birth.…”

Electromagnetic Field Exposure and Male Breast Cancer Risk: A Meta-analysis of 18 Studies

“…Some tentative studies proposed that EMF affected melatonin production in the same way as light in the evening. A suppressive effect of melatonin on estrogen receptor positive breast cancer was found and supported by recent experiments in vitro (Hill et al, 1988;Girgert et al, 2008;Girgert et al, 2010), and researchers indicated that melatonin acted as a potent antioxidant or a protective factor in the immune system (Guerrero et al, 1992;Reiter et al, 1995). Though the relationship between melatonin and breast cancer development had been confirmed in vivo and in vitro experiments, it failed in prospective epidemiological studies (Travis et al, 2004).…”