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Estrogens Cause Rapid Activation of IP3-PKC-α Signal Transduction Pathway in HEPG2 Cells

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Abstract

The mechanisms through which steroids affect target cells are not fully understood. In addition to the classic model, there is now increasing evidence that steroids can exert rapid actions. It must still be elucidated if rapid and slow estrogen actions produce co-operative and/or integrative functions. The effects of estrogen on inositol trisphosphate (IP3) production and PKC-α levels on membrane in the HEPG2 cell line have been investigated. Results show that estrogen addition to HEPG2 cells causes a rapid increase of IP3production. The effect was totally inhibited by pre-incubation with tyrosine-kinase inhibitor genisteine and with the anti-estrogen ICI 182,780. An increased PKC-α level on the membrane fraction was present 30 min after estrogen exposure. The strong signal could elicit a variety of cellular responses such as modulation of ion channel, stimulation of cell proliferation, and phosphorylation of cytosolic ER. The ability of estrogen to trigger IP3production in human hepatoma cells is a novel aspect of estrogen action that requires the current model of hormone stimulation target cells to be revised.

References (25)

  • N.J.G. Webster et al.

    Cell

    (1988)
  • R. Clarke et al.

    Trends Endocrinol. Metab.

    (1996)
  • S. Batra

    Eur. J. Pharmacol.

    (1986)
  • L. Ducher et al.

    Biochem. Biophys. Res. Commun.

    (1995)
  • A. Kumar et al.

    J. Lipid Res.

    (1997)
  • S.M. Cowley et al.

    J. Biol. Chem.

    (1997)
  • A. De Cupis et al.

    Trends in Pharmacol. Sci.

    (1997)
  • J.R. Palmer et al.

    Am. J. Epidemiol.

    (1989)
  • J.J. Li et al.

    Hormonal Carcinogenesis

    (1992)
  • P. Morley et al.

    Endocrinol.

    (1992)
  • S.M. Aronica et al.

    Proc. Natl. Acad. Sci. USA

    (1994)
  • A. Migliaccio et al.

    EMBO J.

    (1996)
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    Li, J. J.Nandi, S.Li, S. A.

    1

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