Related Experiment Videos
Transcriptional repression of RORalpha activity in human breast cancer cells by melatonin
1Department of Structural and Cellular Biology, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
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.
Insights
Melatonin inhibits breast cancer cell growth by affecting retinoid orphan receptor alpha (RORalpha) activity. This occurs through the calcium/calmodulin signaling pathway, impacting RORalpha-regulated genes.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Melatonin is known to inhibit MCF-7 human breast cancer cell proliferation.
- Melatonin's mechanisms of action involve G-protein coupled membrane receptors or retinoid orphan receptors (RORalphas).
Purpose of the Study:
- To investigate the role of RORalpha in melatonin's effect on MCF-7 cells.
- To explore the involvement of the Ca2+/CaM signaling pathway in RORalpha regulation by melatonin.
Main Methods:
- Demonstrated expression of RORalpha2, 3, and 4 transcripts in MCF-7 cells.
- Assessed RORalpha transcriptional activity, DNA-binding activity, and protein levels.
- Investigated the impact of melatonin and Ca2+/CaM signaling pathway modulators.
Main Results:
- MCF-7 cells express RORalpha2, 3, and 4 transcripts with high basal RORalpha transcriptional activity.
- Melatonin repressed RORalpha transactivation and DNA-binding activity in serum-stimulated MCF-7 cells without altering RORalpha protein levels.
- RORalpha transcriptional activity was modulated by Ca2+/CaM signaling pathway modulators.
Conclusions:
- Melatonin may inhibit breast cancer cell proliferation by modulating RORalpha transcriptional activity via the Ca2+/CaM signaling pathway.
- This pathway influences RORalpha-regulated gene expression, offering a potential therapeutic target.