Involvement of the mt1 melatonin receptor in human breast cancer.
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.
Ram
P T
PT
Department of Structural and Cellular Biology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
Dai
J
J
Yuan
L
L
Dong
C
C
Kiefer
T L
TL
Lai
L
L
Hill
S M
SM
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D002227:Carbazoles / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D044094:Receptors, Melatonin; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013844:Thiazoles / Q000494:pharmacology; D013882:Thiosemicarbazones / Q000494:pharmacology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D002227:Carbazoles; C102697:N-acetyl-4-aminomethyl-6-methoxy-9-methyl-1,2,3,4-tetrahydrocarbazole; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; D012333:RNA, Messenger; C539738:RORA protein, human; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D011993:Recombinant Fusion Proteins; D013844:Thiazoles; D013882:Thiosemicarbazones; D015534:Trans-Activators; C092451:CGP 52608; D008156:Luciferases; D008550:Melatonin