Investigations on the mechanisms change and growth of mammary gland tumor cells under the influence of antiestrogenic drugs and low-frequency magnetic fields

In the present project we investigated the molecular mechanism of the decreased antiproliferative effect of the antiestrogenic drug Tamoxifen and the pineal gland hormone Melatonin on breast cancer cells in the presence of low-frequency electromagnetic fields. New unique incubators were developed for the exposure of the cells to controlled, highly homogenous magnetic fields. MCF-7 p40 cells exposed to 1.2 μT expressed 20 genes more than two times stronger than control cells, MCF-7p181 cells 61 genes. 16 genes were expressed weaker in MCF-7p40 cells, 41 genes in MCF-7p181. The increased expression of the particularly interesting coactivators, AIB1 and SRC-1, and of urokinase plasminogen activator and plasminogen-activator inhibitor was confirmed using RT-PCR and Western blot. The corepressors, N-Cor and SMRT, and various metastasis-suppressor genes were expressed lower in the exposed cells. Investigations of signal transduction revealed only MAP-kinase Erk1 being more strongly activated after one hour exposure to the magnetic field, while stress-activated MAP-kinases, junK and p38, were not activated by the magnetic field or even slightly deactivated. Experiments on Melatonin action in the magnetic field showed that expression of the two Melatonin receptors, MT1 and RZRα, was only marginally altered at 1,2 μT. Of the target genes of Melatonin expression of tumorsuppressors p53 and p21waf was decreased in the magnetic field whereas the decrease in expression of BRCA1 and c-myc by Melatonin was less strong in the magnetic field.