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Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium.

Publication ,  Journal Article
Improta-Brears, T; Whorton, AR; Codazzi, F; York, JD; Meyer, T; McDonnell, DP
Published in: Proc Natl Acad Sci U S A
April 13, 1999

Estrogens and growth factors such as epidermal growth factor (EGF) act as mitogens promoting cellular proliferation in the breast and in the reproductive tract. Although it was considered originally that these agents manifested their mitogenic actions through separate pathways, there is a growing body of evidence suggesting that the EGF and estrogen-mediated signaling pathways are intertwined. Indeed, it has been demonstrated recently that 17beta-estradiol (E2) can induce a rapid activation of mitogen-activated protein kinase (MAPK) in mammalian cells, an event that is independent of both transcription and protein synthesis. In this study, we have used a pharmacological approach to dissect this novel pathway in MCF-7 breast cancer cells and have determined that in the presence of endogenous estrogen receptor, activation of MAPK by E2 is preceded by a rapid increase in cytosolic calcium. The involvement of intracellular calcium in this process was supported by the finding that the presence of EGTA and Ca2+-free medium did not affect the activation of MAPK by E2 and, additionally, that this response was blocked by the addition of the intracellular calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate. Cumulatively, these data indicate that the estrogen receptor, in addition to functioning as a transcription factor, is also involved, through a nongenomic mechanism, in the regulation of both intracellular calcium homeostasis and MAPK-signaling pathways. Although nongenomic actions of estrogens have been suggested by numerous studies in the past, the ability to link estradiol and the estrogen receptor to a well defined signaling pathway strongly supports a physiological role for this activity.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 13, 1999

Volume

96

Issue

8

Start / End Page

4686 / 4691

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Humans
  • Hela Cells
  • HeLa Cells
  • Fulvestrant
  • Female
 

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Improta-Brears, T., Whorton, A. R., Codazzi, F., York, J. D., Meyer, T., & McDonnell, D. P. (1999). Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium. Proc Natl Acad Sci U S A, 96(8), 4686–4691. https://doi.org/10.1073/pnas.96.8.4686
Improta-Brears, T., A. R. Whorton, F. Codazzi, J. D. York, T. Meyer, and D. P. McDonnell. “Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium.Proc Natl Acad Sci U S A 96, no. 8 (April 13, 1999): 4686–91. https://doi.org/10.1073/pnas.96.8.4686.
Improta-Brears T, Whorton AR, Codazzi F, York JD, Meyer T, McDonnell DP. Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4686–91.
Improta-Brears, T., et al. “Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium.Proc Natl Acad Sci U S A, vol. 96, no. 8, Apr. 1999, pp. 4686–91. Pubmed, doi:10.1073/pnas.96.8.4686.
Improta-Brears T, Whorton AR, Codazzi F, York JD, Meyer T, McDonnell DP. Estrogen-induced activation of mitogen-activated protein kinase requires mobilization of intracellular calcium. Proc Natl Acad Sci U S A. 1999 Apr 13;96(8):4686–4691.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

April 13, 1999

Volume

96

Issue

8

Start / End Page

4686 / 4691

Location

United States

Related Subject Headings

  • Tumor Cells, Cultured
  • Recombinant Proteins
  • Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 3
  • Mitogen-Activated Protein Kinase 1
  • Humans
  • Hela Cells
  • HeLa Cells
  • Fulvestrant
  • Female