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Melatonin blocks the activation of estrogen receptor for DNA binding
Author(s) -
Rato Avelina García,
Pedrero Juana García,
Martínez M. Arántzazu,
Del Rio Beatriz,
Lazo Pedro S.,
Ramos Sofía
Publication year - 1999
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.13.8.857
Subject(s) - melatonin , estrogen receptor , melatonin receptor , estrogen , medicine , estrogen receptor beta , estrogen related receptor alpha , estrogen related receptor gamma , nuclear receptor , endocrinology , estrogen receptor alpha , receptor , chemistry , gper , hormone response element , biology , biochemistry , transcription factor , cancer , breast cancer , gene
The present study shows that melatonin prevents, within the first cell cycle, the estradiol‐induced growth of synchronized MCF7 breast cancer cells. By using nuclear extracts of these cells, we first examined the binding of estradiol–estrogen receptor complexes to estrogen‐responsive elements and found that the addition of estradiol to whole cells activates the binding of the estrogen receptor to DNA whereas melatonin blocks this interaction. By contrast, melatonin neither affects the binding of estradiol to its receptor nor the receptor nuclear localization. Moreover, we also show that addition of estradiol to nuclear extracts stimulates the binding of estrogen receptor to DNA, but this activation is also prevented by melatonin. The inhibitory effect caused by melatonin is saturable at nanomolar concentrations and does not appear to be mediated by RZR nuclear receptors. The effect is also specific, since indol derivatives do not cause significant inhibition. Furthermore, we provide evidence that melatonin does not interact with the estrogen receptor in the absence of estradiol. Together, these results demonstrate that melatonin interferes with the activation of estrogen receptor by estradiol. The effect of melatonin suggests the presence of a receptor that, upon melatonin addition, destabilizes the binding of the estradiol–estrogen receptor complex to the estrogen responsive element.—Rato, A. G., Pedrero, J. G., Martínez, M. A., del Rio, B., Lazo, P. S., Ramos, S. Melatonin blocks the activation of estrogen receptor for DNA binding. FASEB J. 13, 857–868 (1999)