title: Organic anion transporting polypeptide 2B1 expression correlates with uptake of estrone-3-sulfate and cell proliferation in estrogen receptor-positive breast cancer cells.
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.
authors: 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.
authors: Jun
authors: J
authors: Matsumoto
authors: 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.
authors: Noritaka
authors: N
authors: Ariyoshi
authors: Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Masahiro
authors: M
authors: Sakakibara
authors: Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa, Japan.
authors: Takeo
authors: T
authors: Nakanishi
authors: Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Yoshiyuki
authors: Y
authors: Okubo
authors: Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Nobumitsu
authors: N
authors: Shiina
authors: Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Kaoru
authors: K
authors: Fujisaki
authors: Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Takeshi
authors: T
authors: Nagashima
authors: Department of Diagnostic Pathology, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Yukio
authors: Y
authors: Nakatani
authors: Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa, Japan.
authors: Ikumi
authors: I
authors: Tamai
authors: Department of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan.
authors: Harumi
authors: H
authors: Yamada
authors: Department of Pharmaceutical Sciences, International University of Health and Welfare, Tochigi, Japan.
authors: Hiroshi
authors: H
authors: Takeda
authors: Department of Clinical Pharmacology, Chiba University Graduate School of Pharmaceutical Sciences, Chiba, Japan; Division of Pharmacy, Chiba University Hospital, Chiba, Japan.
authors: Itsuko
authors: I
authors: Ishii
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000187:drug effects / Q000378:metabolism*; D004970:Estrone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D061986:MCF-7 Cells; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation
chemical_list: C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D019394:Ki-67 Antigen; D027361:Organic Anion Transporters; D012333:RNA, Messenger; C450859:SLCO2B1 protein, human; D004970:Estrone; D004958:Estradiol; C017296:estrone sulfate
keywords: Breast cancer; Estrogen receptor; Estrone-3-sulfate; Ki-67; Luminal A-like; Luminal B-Like; Organic anion-transporting polypeptide 2B1