MELATONIN MODULATION OF ESTROGEN-RECEPTOR EXPRESSION IN MCF-7 HUMAN BREAST-CANCER CELLS

MCF-7 human breast cancer cells, which are estrogen receptor (ER)-positive and responsive to the mitogenic actions of estrogen, were used to examine the possible association between the growth-inhibitory activity of melatonin and its ability to modulate the estrogen-response pathway. Melatonin at physiologic concentrations (10(-8)-10(-11) M) significantly decreased estrogen binding activity and the expression of immunoreactive ER in a dose-specific and time-dependent manner. However, melatonin did not alter receptor affinity and was unable to compete with estrogen for binding to the ER. Studies in a yeast trancriptional assay system confirmed that melatonin does not directly bind to the ER to modulate ER expression. Thus, it appears that the antimitotic actions of melatonin may be mediated, at least in part, through the suppression of the estrogen-response pathway of MCF-7 cells.