Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells
- Cite this article as:
- Kiefer, T., Ram, P.T., Yuan, L. et al. Breast Cancer Res Treat (2002) 71: 37. doi:10.1023/A:1013301408464
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We have previously demonstrated that the pineal hormone, melatonin, can inhibit the growth of estrogen receptor-alpha (ERα)-positive breast cancer cells and suppress ERα gene transcription. To investigate the relationship between the estrogen response pathway and melatonin's growth inhibition, ERα-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-β-estradiol (E2) or treated with each compound alone. Melatonin pre-treatment significantly reduced E2-induced ERα transactivation and ERα-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 ERα transcriptional activity by regulating signal transduction pathways which impinge on the ERα and by altering E2-mediated ERα transactivation and ERα DNA binding activity.