Abstract:
:Melatonin has repeatedly been shown to inhibit the proliferation of MCF-7 human breast cancer cells. Previous reports suggest that the actions of melatonin can be mediated either through G-protein coupled membrane receptors or via retinoid orphan receptors (RORalphas). In this study, we demonstrated the expression of RORalpha2, 3, and 4 transcripts in MCF-7 cells. These cells exhibited a high basal level of RORalpha transcriptional activity, which was further stimulated by serum. In the presence of serum, RORalpha transactivation and DNA-binding activity was repressed by melatonin even though melatonin had no effect on RORalpha protein levels. We found that RORalpha 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 RORalpha transcriptional activity, expression of RORalpha regulated genes, and even breast cancer cell proliferation via modulation of the Ca2+/CaM signaling pathway.
journal_name
Mol Cell Endocrinoljournal_title
Molecular and cellular endocrinologyauthors
Dai J,Ram PT,Yuan L,Spriggs LL,Hill SMdoi
10.1016/s0303-7207(01)00449-xkeywords:
subject
Has Abstractpub_date
2001-05-15 00:00:00pages
111-20issue
1-2eissn
0303-7207issn
1872-8057pii
S030372070100449Xjournal_volume
176pub_type
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