Breast Cancer Research and Treatment

, Volume 71, Issue 1, pp 37–45

Melatonin inhibits estrogen receptor transactivation and cAMP levels in breast cancer cells

  • T. Kiefer
  • P. T. Ram
  • L. Yuan
  • S. M. Hill
Article

DOI: 10.1023/A:1013301408464

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

Abstract

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.

breast cancercAMPestrogen receptormelatonin

Copyright information

© Kluwer Academic Publishers 2002

Authors and Affiliations

  • T. Kiefer
    • 1
    • 2
  • P. T. Ram
    • 1
  • L. Yuan
    • 1
  • S. M. Hill
    • 1
    • 3
    • 2
  1. 1.Department of Structural and Cellular BiologyUSA
  2. 2.Graduate Program in Molecular and Cellular BiologyTulane University School of MedicineNew OrleansUSA
  3. 3.Tulane Cancer CenterUSA