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

Autor: Matsumoto J; Department of Clinical Pharmacology, Chiba University Graduate School of Pharmaceutical Sciences, Chiba, Japan; Department of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan., Ariyoshi N; Department of Clinical Pharmacology, Chiba University Graduate School of Pharmaceutical Sciences, Chiba, Japan; Division of Pharmacy, Chiba University Hospital, Chiba, Japan. Electronic address: ariyoshi@ho.chiba-u.ac.jp., Sakakibara M; Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Nakanishi T; Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa, Japan., Okubo Y; Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Shiina N; Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Fujisaki K; Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Nagashima T; Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan., Nakatani Y; Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan., Tamai I; Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa, Japan., Yamada H; Department of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan., Takeda H; Department of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan., Ishii I; Department of Clinical Pharmacology, Chiba University Graduate School of Pharmaceutical Sciences, Chiba, Japan; Division of Pharmacy, Chiba University Hospital, Chiba, Japan.
Jazyk: angličtina
Zdroj: Drug metabolism and pharmacokinetics [Drug Metab Pharmacokinet] 2015 Apr; Vol. 30 (2), pp. 133-41. Date of Electronic Publication: 2014 Nov 14.
DOI: 10.1016/j.dmpk.2014.10.005
Abstrakt: 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.
(Copyright © 2014 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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