Organic anion transporting polypeptide 2B1 expression correlates with uptake of estrone-3-sulfate and cell proliferation in estrogen receptor-positive breast cancer cells

Jun Matsumoto, Noritaka Ariyoshi, Masahiro Sakakibara, Takeo Nakanishi, Yoshiyuki Okubo, Nobumitsu Shiina, Kaoru Fujisaki, Takeshi Nagashima, Yukio Nakatani, Ikumi Tamai, Harumi Yamada, Hiroshi Takeda, Itsuko Ishii

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9 Citations (Scopus)


Abstract Estrone-3-sulfate (E1S) is thought to be a major estrogen precursor in estrogen receptor (ER)-positive breast cancer. Since E1S is a hydrophilic compound, the uptake of E1S into cancer cells is probably mediated by transporters, such as organic anion-transporting polypeptide (OATP, SLCO) family. In this study, we investigated the relationship between expression of OATP2B1 and cell proliferation in ER-positive breast cancer. Cell-based assays were carried out in MCF-7 cells both with and without overexpression of OATP2B1. Normal breast and tumor tissues were collected and used in this study. Cell proliferation, ER-mediated transcriptional activities and estradiol secretion were stimulated by addition of E1S to the culture medium of MCF-7 cells. These stimulatory effects were significantly greater in MCF-7 cells overexpressing OATP2B1 than in control cells. The expression level of SLCO2B1 mRNA was significantly correlated with histological grade, Ki-67 labelling index and mRNA expression of steroid sulfatase. The expression level of SLCO2B1 mRNA in luminal B-like cancers was higher than that in luminal A-like cancers. Uptake of E1S resulted in down-regulation of ERα protein and induction of Ki-67 in MCF-7 cells. The present study suggests that OATP2B1 is involved in cell proliferation by increasing the amount of estrogen in ER-positive breast cancer cells.

Original languageEnglish
Article number13
Pages (from-to)133-141
Number of pages9
JournalDrug Metabolism And Pharmacokinetics
Issue number2
Publication statusPublished - Jan 4 2015
Externally publishedYes



  • Breast cancer
  • Estrogen receptor
  • Estrone-3-sulfate
  • Ki-67
  • Luminal A-like
  • Luminal B-Like
  • Organic anion-transporting polypeptide 2B1

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Pharmacology (medical)

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