title: Molecular deficiency (ies) in MT₁ melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells.
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.
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA, USA; Tulane Cancer Center and Louisiana Cancer Research Consortium, New Orleans, LA, USA.
authors.forename: Lulu
authors.initials: L
authors.lastname: Mao
authors.forename: Lin
authors.initials: L
authors.lastname: Yuan
authors.forename: Shulin
authors.initials: S
authors.lastname: Xiang
authors.forename: Samantha B
authors.initials: SB
authors.lastname: Zeringue
authors.forename: Robert T
authors.initials: RT
authors.lastname: Dauchy
authors.forename: David E
authors.initials: DE
authors.lastname: Blask
authors.forename: Adam
authors.initials: A
authors.lastname: Hauch
authors.forename: Steven M
authors.initials: SM
authors.lastname: Hill
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010641:Phenotype; D044122:Receptor, Melatonin, MT1 / Q000235:genetics* / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D044122:Receptor, Melatonin, MT1; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D008550:Melatonin
keywords: melatonin; melatonin receptor (MT1)