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Laboratory for Molecular Gynecology
Head: Prof. Dr. rer. nat. Carsten Gründker
Dept. Gynecology and Obstetrics
Chairman: Prof. Dr. med. Günter Emons

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Last Modification:
11.01.2013

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Melatonin and Breast Cancer
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Breast cancer is the most frequent malignant disease in women. There is good evidence that the pineal gland influences the development and growth of breast cancer by its major hormone melatonin. Melatonin has been shown to possess an antiestrogenic effect on estrogen receptor expressing (ER+) breast cancer cells in culture by reducing cell cycle progression and cell proliferation. There is increasing agreement that on cellular level the effects of melatonin are primarily induced by the membrane bound receptor MT1. The participation of a second, nuclear receptor of the group of ligand-dependent transcription factors, called RZRalpha, is under debate. We used a number of breast cancer cell lines differing in their expression of the estrogen receptor and the two known melatonin receptors. In MCF-7 breast cancer cells transfected with a vector carrying the MT1 gene (MCF-7Mel1a) the binding of the CREB protein to the cAMP responsive element of the breast cancer suppressing gene BRCA-1 was more strongly reduced by treatment with melatonin than in the parental cells. Expression of estrogen responsive genes was determined in serum starved cells, cells stimulated for 16 hours with estradiol and cells subsequently treated with melatonin. Expression of BRCA-1, p53, p21WAF and c-myc were up-regulated by estradiol and treatment of the stimulated cells with melatonin counteracted the increase by estradiol almost completely. The more MT1 a cell line expressed the stronger was the reduction of the expression of the estradiol induced genes. There was no correlation between the expression of the nuclear receptor RZRalpha and the effects of melatonin on these genes.

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