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Involvement of the mt1 melatonin receptor in human breast cancer
1Department of Structural and Cellular Biology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Abstract:
Two putative melatonin receptors have been described including the cell surface G-protein-linked receptors, mt1 and MT2, and the nuclear retinoic orphan receptor alpha (RORalpha). The mt1 receptor, but not the MT2 receptor, is expressed in human breast tumor cell lines, and melatonin-induced growth suppression can be mimicked by the mt1 and MT2 agonist, AMMTC, and blocked by the antagonist, CBPT. RORalpha receptors are also expressed in MCF-7 breast cancer cells and the putative RORalpha agonist CPG-52608 inhibits MCF-7 cell growth but with a very different dose-response than melatonin. Finally, melatonin and AMMTC, but not CPG-52608, can repress RORalpha transcriptional activity in MCF-7 cells.
Insights
Melatonin receptors, mt1 and MT2, are found in breast tumor cells. Melatonin and its agonist suppress tumor growth, but the nuclear receptor RORalpha
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Background:
- Two melatonin receptors, cell surface mt1/MT2 and nuclear RORalpha, are known.
- mt1 receptor is present in human breast tumor cell lines.
- RORalpha receptors are also expressed in MCF-7 breast cancer cells.
Purpose of the Study:
- To investigate the roles of mt1, MT2, and RORalpha receptors in melatonin's effects on breast cancer cells.
- To determine the specific receptor mediating melatonin-induced growth suppression.
- To explore the interaction between melatonin signaling and RORalpha activity.
Main Methods:
- Utilized human breast tumor cell lines (MCF-7).
- Administered melatonin, mt1/MT2 agonist (AMMTC), antagonist (CBPT), and RORalpha agonist (CPG-52608).
- Assessed cell growth suppression and RORalpha transcriptional activity.
Main Results:
- mt1 receptor, not MT2, is expressed in breast tumor cells.
- Melatonin-induced growth suppression mimicked by AMMTC and blocked by CBPT.
- CPG-52608 inhibited MCF-7 cell growth differently than melatonin.
- Melatonin and AMMTC repressed RORalpha transcriptional activity, but CPG-52608 did not.
Conclusions:
- The mt1 receptor mediates melatonin's growth-suppressive effects in breast cancer cells.
- Melatonin signaling pathways interact with and can repress RORalpha transcriptional activity.
- Findings suggest distinct roles for cell surface and nuclear melatonin receptors in breast cancer.