Membrane-bound melatonin receptor MT1 down-regulates estrogen responsive genes in breast cancer cells

被引:58
作者
Girgert, Rainer [1 ,2 ]
Hanf, Volker [3 ]
Emons, Guenter [1 ]
Gruendker, Carsten [1 ]
机构
[1] Univ Gottingen, Dept Obstet & Gynecol, D-37075 Gottingen, Germany
[2] Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany
[3] Klinikum Furth, Dept Obstet & Gynecol, Furth, Germany
关键词
breast cancer; estrogen responsive genes; gene expression; melatonin receptors; signal transduction; NUCLEAR RECEPTOR; BRCA1; EXPRESSION; PINEAL HORMONE; C-MYC; P53; MCF-7; PROTEINS; GROWTH; PROMOTER; CYCLE;
D O I
10.1111/j.1600-079X.2009.00684.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:23 / 31
页数:9
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