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Uptake transporter organic anion transporting polypeptide 1B3 contributes to the growth of estrogen-dependent breast cancer.

Abstract
Estrone-3-sulfate is one of the most abundant estrogen precursors in postmenopausal women. We previously showed that estrone-3-sulfate transporters are present in human breast cancer-derived MCF-7 cells (J. Pharmacol. Exp. Ther. 311 (2004) 1032-1037) and that inhibition of estrone-3-sulfate uptake resulted in the suppression of cell growth (Pharm. Res. 22 (2005) 1634-1641); therefore, estrone-3-sulfate transporter should be a novel target for therapy of hormone-dependent breast cancers. The purpose of the present study is to identify the transporter(s) responsible for the uptake of estrone-3-sulfate in breast cancer cells. We obtained two subclones of MCF-7 cells with different estrone-3-sulfate uptake activities and searched for differentially expressed transporter genes by means of DNA microarray analysis. Among several candidate transporters identified, OATP1B3 was further evaluated, since the uptake characteristics of estrone-3-sulfate by MCF-7 cells seemed consistent with the transport properties of OATP1B3. The contribution of OATP1B3 to estrone-3-sulfate uptake by MCF-7 cells was examined by the relative activity factor (RAF) method, and was calculated to amount to 6%. This result suggests that OATP1B3 is one of the transporters contributing to the supply of the estrogen precursor estrone-3-sulfate to estrogen-dependent breast cancer cells.
AuthorsTomoji Maeda, Masanori Irokawa, Hiroshi Arakawa, Erika Kuraoka, Takashi Nozawa, Ryoko Tateoka, Yoshiharu Itoh, Takeo Nakanishi, Ikumi Tamai
JournalThe Journal of steroid biochemistry and molecular biology (J Steroid Biochem Mol Biol) Vol. 122 Issue 4 Pg. 180-5 (Oct 2010) ISSN: 1879-1220 [Electronic] England
PMID20615467 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2010 Elsevier Ltd. All rights reserved.
Chemical References
  • Organic Anion Transporters, Sodium-Independent
  • SLCO1B3 protein, human
  • Estrone
  • estrone sulfate
Topics
  • Animals
  • Biological Transport
  • Breast Neoplasms (genetics, metabolism)
  • Cell Line, Tumor
  • Cell Proliferation
  • Estrone (analogs & derivatives, metabolism)
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Organic Anion Transporters, Sodium-Independent (genetics, metabolism)
  • Xenopus laevis

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