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Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors.

Publication ,  Journal Article
Ram, PT; Kiefer, T; Silverman, M; Song, Y; Brown, GM; Hill, SM
Published in: Mol Cell Endocrinol
June 25, 1998

The pineal hormone, melatonin, inhibits proliferation of estrogen receptor (ER)-positive MCF-7 human breast cancer cells, modulates both ER mRNA and protein expression, and appears to be serum dependent, indicating interaction between melatonin and serum components. To examine the effects of melatonin on ER activity, ER transactivation assays were performed by transiently transfecting MCF-7 cells with an ERE-luciferase reporter construct. MCF-7 cells pre-treated with melatonin for as little as 5 min followed by either epidermal growth factor (EGF) or insulin resulted in the estrogen-independent transactivation of the ER. None of the compounds when used alone transactivated the ER. The ability of melatonin and EGF to transactivate the ER was abolished by the addition of the antiestrogen, ICI 164384, suggesting that melatonin and EGF co-operate to transactivate the ER. The modulation of ER transactivation was associated with changes in mitogen activated protein kinase activity and ER phosphorylation. This ER transactivation was blocked by pertussis toxin, a Galpha i-protein-coupled receptor inhibitor, suggesting cross talk between the G-protein-coupled melatonin receptor pathway and the EGF/insulin tyrosine kinase receptor pathways in modulating ER transactivation. Exactly how the ability of melatonin in combination with EGF to transactivate the ER relates to melatonin's observed growth suppressive effects is not clear. It is possible that, although melatonin and EGF transactivate the ER, this transactivation does not result in the full transcription of estrogen-responsive genes, but rather, makes the ER refractory to activation by estradiol, thus, blocking the mitogenic actions of estradiol.

Duke Scholars

Published In

Mol Cell Endocrinol

DOI

ISSN

0303-7207

Publication Date

June 25, 1998

Volume

141

Issue

1-2

Start / End Page

53 / 64

Location

Ireland

Related Subject Headings

  • Virulence Factors, Bordetella
  • Tumor Cells, Cultured
  • Transfection
  • Transcriptional Activation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Melatonin
  • Receptors, Estrogen
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Cell Surface
  • Polyunsaturated Alkamides
 

Citation

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Ram, P. T., Kiefer, T., Silverman, M., Song, Y., Brown, G. M., & Hill, S. M. (1998). Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors. Mol Cell Endocrinol, 141(1–2), 53–64. https://doi.org/10.1016/s0303-7207(98)00095-1
Ram, P. T., T. Kiefer, M. Silverman, Y. Song, G. M. Brown, and S. M. Hill. “Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors.Mol Cell Endocrinol 141, no. 1–2 (June 25, 1998): 53–64. https://doi.org/10.1016/s0303-7207(98)00095-1.
Ram PT, Kiefer T, Silverman M, Song Y, Brown GM, Hill SM. Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors. Mol Cell Endocrinol. 1998 Jun 25;141(1–2):53–64.
Ram, P. T., et al. “Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors.Mol Cell Endocrinol, vol. 141, no. 1–2, June 1998, pp. 53–64. Pubmed, doi:10.1016/s0303-7207(98)00095-1.
Ram PT, Kiefer T, Silverman M, Song Y, Brown GM, Hill SM. Estrogen receptor transactivation in MCF-7 breast cancer cells by melatonin and growth factors. Mol Cell Endocrinol. 1998 Jun 25;141(1–2):53–64.
Journal cover image

Published In

Mol Cell Endocrinol

DOI

ISSN

0303-7207

Publication Date

June 25, 1998

Volume

141

Issue

1-2

Start / End Page

53 / 64

Location

Ireland

Related Subject Headings

  • Virulence Factors, Bordetella
  • Tumor Cells, Cultured
  • Transfection
  • Transcriptional Activation
  • Reverse Transcriptase Polymerase Chain Reaction
  • Receptors, Melatonin
  • Receptors, Estrogen
  • Receptors, Cytoplasmic and Nuclear
  • Receptors, Cell Surface
  • Polyunsaturated Alkamides