Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells.
We have previously demonstrated that the pineal hormone, melatonin, can inhibit the growth of estrogen receptor-alpha (ERalpha)-positive breast cancer cells and suppress ERalpha gene transcription. To investigate the relationship between the estrogen response pathway and melatonin's growth inhibition, ERalpha-positive MCF-7 human breast cancer cells were transiently transfected with an estrogen response element (ERE) luciferase reporter construct and then treated with melatonin (10(-9)-10(-6) M) for 30 min followed by 10(-9) M 17-beta-estradiol (E2) or treated with each compound alone. Melatonin pre-treatment significantly reduced E2-induced ERalpha transactivation and ERalpha-ERE binding activity. We also conducted experiments to determine if melatonin modulates cAMP levels in MCF-7 cells. Melatonin inhibited the forskolin-induced and E2-induced elevation of cAMP levels by 57 and 45%, respectively. These data indicate that melatonin can act as a biological modifier to affect ERalpha transcriptional activity by regulating signal transduction pathways which impinge on the ERalpha and by altering E2-mediated ERalpha transactivation and ERalpha DNA binding activity.
Kiefer
T
T
Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Ram
P T
PT
Yuan
L
L
Hill
S M
SM
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000473:pathology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D011960:Receptors, Estrogen / Q000096:biosynthesis*; D015398:Signal Transduction; D014162:Transfection; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D047628:Estrogen Receptor alpha; D011960:Receptors, Estrogen; D004958:Estradiol; D000242:Cyclic AMP; D008550:Melatonin