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Research ArticleCHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

Involvement of Estrone-3-Sulfate Transporters in Proliferation of Hormone-Dependent Breast Cancer Cells

Takashi Nozawa, Masato Suzuki, Koichi Takahashi, Hikaru Yabuuchi, Tomoji Maeda, Akira Tsuji and Ikumi Tamai
Journal of Pharmacology and Experimental Therapeutics December 2004, 311 (3) 1032-1037; DOI: https://doi.org/10.1124/jpet.104.071522
Takashi Nozawa
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Masato Suzuki
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Koichi Takahashi
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Hikaru Yabuuchi
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Tomoji Maeda
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Akira Tsuji
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Ikumi Tamai
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Abstract

Although circulating estrone-3-sulfate is a major precursor of biologically active estrogen, permeation across the plasma membrane is unlikely to occur by diffusion because of the high hydrophilicity of the molecule. The object of this study was to clarify the involvement of specific transporter(s) in the supply of estrone-3-sulfate to human breast cancer-derived T-47D cells, which grow in an estrogen-dependent manner. The proliferation of T-47D cells was increased by the addition of estrone-3-sulfate, or estradiol, to the cultivation medium. The initial uptake rate of estrone-3-sulfate kinetically exhibited a single saturable component, with Km and Vmax values of 7.6 μM and 172 pmol/mg of protein/min, respectively. The replacement of extracellular Na+ with Li+, K+, or N-methylglucamine+ had no effect on the uptake of [3H]estrone-3-sulfate. The uptake was strongly inhibited by sulfate conjugates of steroid hormones, but not by estradiol-17β-glucuronide. Taurocholate and sulfobromophthalein inhibited the uptake, whereas other tested anionic and cationic compounds did not. The expression of organic anion transporting polypeptides, OATP-D and OATP-E, which are candidate transporters of estrone-3-sulfate, was detected by reverse transcription-polymerase chain reaction analysis, although their actual involvement in the uptake of estrogen remains to be clarified. In conclusion, the uptake of estrone-3-sulfate by T-47D cells was mediated by a carrier-mediated transport mechanism, suggesting that the estrogen precursor is actively imported by estrogen-dependent breast cancer cells.

Footnotes

  • This project was financially supported in part by the Ministry of Education, Culture, Sports, Science, and Technology, Japan (grant-in-aid for scientific research).

  • doi:10.1124/jpet.104.071522.

  • ABBREVIATIONS: OAT, organic anion transporter; OATP, organic anion transporting polypeptide; FCS, fetal calf serum; DCC, dextran-coated charcoal; DMSO, dimethyl sulfoxide; RT-PCR, reverse transcription-polymerase chain reaction; DHEAS, dehydroepiandrosterone sulfate.

    • Received May 18, 2004.
    • Accepted August 20, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 311 (3)
Journal of Pharmacology and Experimental Therapeutics
Vol. 311, Issue 3
1 Dec 2004
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Research ArticleCHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

Involvement of Estrone-3-Sulfate Transporters in Proliferation of Hormone-Dependent Breast Cancer Cells

Takashi Nozawa, Masato Suzuki, Koichi Takahashi, Hikaru Yabuuchi, Tomoji Maeda, Akira Tsuji and Ikumi Tamai
Journal of Pharmacology and Experimental Therapeutics December 1, 2004, 311 (3) 1032-1037; DOI: https://doi.org/10.1124/jpet.104.071522

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Research ArticleCHEMOTHERAPY, ANTIBIOTICS, AND GENE THERAPY

Involvement of Estrone-3-Sulfate Transporters in Proliferation of Hormone-Dependent Breast Cancer Cells

Takashi Nozawa, Masato Suzuki, Koichi Takahashi, Hikaru Yabuuchi, Tomoji Maeda, Akira Tsuji and Ikumi Tamai
Journal of Pharmacology and Experimental Therapeutics December 1, 2004, 311 (3) 1032-1037; DOI: https://doi.org/10.1124/jpet.104.071522
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