ABSTRACT: Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells T. Kiefer,P.T.Ram, L.Yuan,S.M. Hill We have previously demonstrated that the pineal hormone, melatonin, can inhibit the growth of estrogen receptor-alpha (ER-alpha)-positive breast cancer cells and suppress ER-alpha gene transcription. To investigate the relationship between the estrogen response pathway and melatonin's growth inhibition, ER-alpha-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^-6M) for 30min followed by 10^-9M 17-beta-estradiol (E2) or treated with each compound alone. Melatonin pre-treatment significantly reduced E2-induced ER-alpha transactivation and ER-alpha-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 ER-alpha transcriptional activity by regulating signal transduction pathways which impinge on the ER-alpha and by altering E2-mediated ER-alpha transactivation and ER-alpha DNA binding activity. Breast Cancer Research and Treatment 71(1):37-45, January 2002 J Biol CHem, 9/04 Breast Ca Res & Treat, 12/05 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.