期刊
JOURNAL OF PINEAL RESEARCH
卷 47, 期 1, 页码 23-31出版社
WILEY
DOI: 10.1111/j.1600-079X.2009.00684.x
关键词
breast cancer; estrogen responsive genes; gene expression; melatonin receptors; signal transduction
资金
- German Federal Ministry for Environment, Nature Conservation and Nuclear Safety [StSch4219, StSch4461]
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 RZR alpha, 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 RZR alpha and the effects of melatonin on these genes.
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