The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-β-estradiol and 4-OH estradiol in human breast epithelial cells

  • Authors:
    • Mohamed H. Lareef
    • James Garber
    • Patricia A. Russo
    • Irma H. Russo
    • Rebecca Heulings
    • Jose Russo
  • View Affiliations

  • Published online on: February 1, 2005     https://doi.org/10.3892/ijo.26.2.423
  • Pages: 423-429
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Abstract

Prolonged unopposed estrogen exposure is a widely accepted risk factor in breast cancer development. However, the mechanisms through which estrogens induce breast carcinogenesis have not been definitively unraveled. For testing whether estrogens exert their transforming effects through a non-receptor-mediated mechanism, we have treated the spontaneously immortalized human breast epithelial cells MCF-10F, which are estrogen receptor α negative, with 17-β estradiol (E2) or its metabolite 4-OH-estradiol (4-OH-E2), each one either alone or in combination with the antiestrogen ICI-182-780. Treated cells were maintained for several passages in culture and evaluated for colony formation in agar-methocel (CE), tri-dimensional growth in collagen matrix, invasiveness in matrigel, and cell cycle analysis by flow cytometry. Both E2 and 4-HO-E2, at all the doses tested, in the presence or absence of ICI-182-780, increased CE and decreased the cells' ductulogenic capacity. They also increased the invasiveness and the number of cells in the S phase of the cell cycle. Our data clearly demonstrate that E2 and 4-OH-E2 increase cell proliferation and induce transformation in MCF-10F cells, phenomena that are not abrogated by ICI-182-780. The failure of the antiestrogen to abrogate the transformation phenotypes led us to hypothesize that estrogen-induced transformation is occurring by a non-estrogen receptor α-mediated process, more probably through the genotoxic effect of the estrogen metabolite 4-HO-E2.

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February 2005
Volume 26 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Lareef MH, Garber J, Russo PA, Russo IH, Heulings R and Russo J: The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-β-estradiol and 4-OH estradiol in human breast epithelial cells. Int J Oncol 26: 423-429, 2005.
APA
Lareef, M.H., Garber, J., Russo, P.A., Russo, I.H., Heulings, R., & Russo, J. (2005). The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-β-estradiol and 4-OH estradiol in human breast epithelial cells. International Journal of Oncology, 26, 423-429. https://doi.org/10.3892/ijo.26.2.423
MLA
Lareef, M. H., Garber, J., Russo, P. A., Russo, I. H., Heulings, R., Russo, J."The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-β-estradiol and 4-OH estradiol in human breast epithelial cells". International Journal of Oncology 26.2 (2005): 423-429.
Chicago
Lareef, M. H., Garber, J., Russo, P. A., Russo, I. H., Heulings, R., Russo, J."The estrogen antagonist ICI-182-780 does not inhibit the transformation phenotypes induced by 17-β-estradiol and 4-OH estradiol in human breast epithelial cells". International Journal of Oncology 26, no. 2 (2005): 423-429. https://doi.org/10.3892/ijo.26.2.423