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

MCF-7 human breast cancer cells, which are estrogen receptor (ER)-posi tive and responsive to the mitogenic actions of estrogen, were used to examine the possible association between the growth-inhibitory activi ty of melatonin and its ability to modulate the estrogen-response path way. Melatonin at physiologic concentrations (10(-8)-10(-11) M) signif icantly decreased estrogen binding activity and the expression of immu noreactive ER in a dose-specific and time-dependent manner. However, m elatonin did not alter receptor affinity and was unable to compete wit h estrogen for binding to the ER. Studies in a yeast trancriptional as say system confirmed that melatonin does not directly bind to the ER t o modulate ER expression. Thus, it appears that the antimitotic action s of melatonin may be mediated, at least in part, through the suppress ion of the estrogen-response pathway of MCF-7 cells.