Transcriptional repression of RORα activity in human breast cancer cells by melatonin

Melatonin has repeatedly been shown to inhibit the proliferation of MCF-7 human breast cancer cells. Previous reports suggest that the actions of melatonin call be mediated either through G-protein coupled membrane receptors or via retinoid orphan receptors (ROR alphas). In this study, we demonstrated the expression of ROR alpha2, 3, and 4 transcripts in MCF-7 cells. These cells exhibited a high basal level of ROR alpha transcriptional activity, which was further stimulated by serum. In the presence of serum, RORa transactivation and DNA-binding activity was repressed by melatonin even though melatonin had no effect on ROR alpha protein levels. We found that ROR alpha transcriptional activity in MCF-7 cells was regulated by modulators of the Ca2+/CaM signaling pathway. Given that melatonin has been reported to modulate the Ca2+ /CaM signaling pathway in other tissues, our data indicate that melatonin may affect ROR alpha transcriptional activity, expression of RORa regulated genes, and even breast cancer cell proliferation via modulation of the Ca2+/CaM signaling pathway. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.