Transcriptional repression of ROR alpha activity in human breast cancer cells by melatonin

Melatonin has repeatedly been shown to inhibit the proliferation of MCF-7 h uman breast cancer cells. Previous reports suggest that the actions of mela tonin call be mediated either through G-protein coupled membrane receptors or via retinoid orphan receptors (ROR alphas). In this study, we demonstrat ed 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 trans activation and DNA-binding activity was repressed by melatonin even though melatonin had no effect on ROR alpha protein levels. We found that ROR alph a transcriptional activity in MCF-7 cells was regulated by modulators of th e Ca2+/CaM signaling pathway. Given that melatonin has been reported to mod ulate the Ca2+ /CaM signaling pathway in other tissues, our data indicate t hat melatonin may affect ROR alpha transcriptional activity, expression of RORa regulated genes, and even breast cancer cell proliferation via modulat ion of the Ca2+/CaM signaling pathway. (C) 2001 Elsevier Science Ireland Lt d. All rights reserved.