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Membrane‐bound melatonin receptor MT1 down‐regulates estrogen responsive genes in breast cancer cells
Author(s) -
Girgert Rainer,
Hanf Volker,
Emons Günter,
Gründker Carsten
Publication year - 2009
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2009.00684.x
Subject(s) - melatonin , estrogen receptor , melatonin receptor , medicine , endocrinology , biology , transfection , cancer cell , receptor , cancer research , estrogen , cell culture , estrogen receptor beta , creb , breast cancer , transcription factor , cancer , gene , biochemistry , genetics
Melatonin possesses anti‐estrogenic effects on estrogen receptor expressing (ER+) breast cancer cells in culture by reducing cell cycle progression and cell proliferation. There is increasing agreement that on a 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 RZRα, is under debate. In this study 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) binding of 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 hr with estradiol and cells subsequently treated with melatonin. Expression of BRCA‐1, p53, p21 WAF and c‐myc were up‐regulated by estradiol. Treatment of the stimulated cells with melatonin counteracted the increase induced 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 RZRα and the effects of melatonin on these genes.