Abstract |
Melatonin has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its antiproliferative effects have been well studied in MCF-7 human breast cancer cells and several other estrogen receptor α (ERα)-positive human breast cancer cell lines. However, the MDA-MB-231 breast cancer cell line, an ERα-negative cell line widely used in breast cancer research, has been shown to be unresponsive to melatonin's growth-suppressive effect in vitro. Here, we examined the effect of melatonin on the cell proliferation of several ERα-negative breast cancer cell lines including MDA-MB-231, BT-20, and SK-BR-3 cells. Although the MT1 G-protein-coupled receptor is expressed in all three cell lines, melatonin significantly suppressed the proliferation of SK-BR-3 cells without having any significant effect on the growth of MDA-MB-231 and BT-20 cells. We confirmed that the MT1-associated Gα proteins are expressed in MDA-MB-231 cells. Further studies demonstrated that the melatonin unresponsiveness in MDA-MB-231 cells may be caused by aberrant signaling downstream of the Gαi proteins, resulting in differential regulation of ERK1/2 activity.
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Authors | Lulu Mao, Lin Yuan, Shulin Xiang, Samantha B Zeringue, Robert T Dauchy, David E Blask, Adam Hauch, Steven M Hill |
Journal | Journal of pineal research
(J Pineal Res)
Vol. 56
Issue 3
Pg. 246-53
(Apr 2014)
ISSN: 1600-079X [Electronic] England |
PMID | 24372669
(Publication Type: Journal Article, Research Support, N.I.H., Extramural)
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Copyright | © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. |
Chemical References |
- ESR1 protein, human
- Estrogen Receptor alpha
- Receptor, Melatonin, MT1
- Mitogen-Activated Protein Kinase 1
- Mitogen-Activated Protein Kinase 3
- Melatonin
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Topics |
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Estrogen Receptor alpha
(genetics)
- Female
- Humans
- Melatonin
(pharmacology)
- Mitogen-Activated Protein Kinase 1
(metabolism)
- Mitogen-Activated Protein Kinase 3
(metabolism)
- Phenotype
- Receptor, Melatonin, MT1
(genetics, physiology)
- Signal Transduction
(drug effects)
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