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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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
Volume30
Issue number2
DOIs
Publication statusPublished - Jan 4 2015
Externally publishedYes

    Fingerprint

Keywords

  • 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)

Cite this