MT(1) melatonin receptor overexpression enhances the growth suppressive effect of melatonin in human breast cancer cells.
Melatonin inhibits the proliferation of estrogen receptor alpha (ERalpha)-positive (MCF-7), but not ERalpha-negative (MDA-MB-231) breast cancer cells. Here, we assessed the effect of MT(1) melatonin receptor stable overexpression in MCF-7 and MDA-MB-231 breast cancer cells on the growth-suppressive effects of melatonin. Parental and vector-transfected MCF-7 cells demonstrated a modest, but significant, growth-suppressive response to melatonin; however, melatonin treatment of MT(1)-transfected MCF-7 cells resulted in significantly enhanced growth-suppression. This response was blocked by an MT1/MT2 melatonin receptor antagonist. Interestingly, MT(1)-overexpression did not induce a melatonin-sensitive phenotype in melatonin-insensitive MDA-MB-231 cells. Finally, Northern blot analysis demonstrated an enhanced inhibition of ERalpha mRNA expression and an enhanced induction of pancreatic spasmolytic polypeptide (pS2) by melatonin in MT(1)-transfected MCF-7 cells relative to vector-transfected MCF-7 cells. These data suggest the involvement of the MT(1) melatonin receptor in mediation of melatonin effects on growth-suppression and gene-modulation in breast cancer cells.
Yuan
Lin
L
Department of Structural and Cellular Biology, Tulane University Medical School, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Collins
April R
AR
Dai
Jun
J
Dubocovich
Margarita L
ML
Hill
Steven M
SM
D000230:Adenocarcinoma / Q000737:chemistry / Q000473:pathology*; D001943:Breast Neoplasms / Q000737:chemistry / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D047628:Estrogen Receptor alpha; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008550:Melatonin / Q000494:pharmacology*; D009077:Mucins; D009124:Muscle Proteins; D009281:Naphthalenes / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000032:analysis; D009376:Neoplasms, Hormone-Dependent / Q000737:chemistry / Q000473:pathology*; D009479:Neuropeptides; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011960:Receptors, Estrogen / Q000032:analysis; D044094:Receptors, Melatonin; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; D014407:Tumor Cells, Cultured / Q000737:chemistry / Q000187:drug effects / Q000473:pathology
D047628:Estrogen Receptor alpha; D004967:Estrogens; D006727:Hormone Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D009077:Mucins; D009124:Muscle Proteins; D009281:Naphthalenes; D009363:Neoplasm Proteins; D009479:Neuropeptides; D010455:Peptides; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D011960:Receptors, Estrogen; D044094:Receptors, Melatonin; D011993:Recombinant Fusion Proteins; C099037:TFF3 protein, rat; C000604008:Tff2 protein, rat; D000071164:Trefoil Factor-2; D000071165:Trefoil Factor-3; C106874:N-(2-(1-naphthalenyl)ethyl)cyclobutanecarboxamide; C034407:pancreatic spasmolytic polypeptide; D008550:Melatonin