RRC ID 61893
Author Matsumoto J, Ariyoshi N, Sakakibara M, Nakanishi T, Okubo Y, Shiina N, Fujisaki K, Nagashima T, Nakatani Y, Tamai I, Yamada H, Takeda H, Ishii I.
Title Organic anion transporting polypeptide 2B1 expression correlates with uptake of estrone-3-sulfate and cell proliferation in estrogen receptor-positive breast cancer cells.
Journal Drug Metab Pharmacokinet
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.
Volume 30(2)
Pages 133-41
Published 2015-4-1
DOI 10.1016/j.dmpk.2014.10.005
PII S1347-4367(14)00014-7
PMID 25857231
MeSH Breast Neoplasms / genetics Breast Neoplasms / metabolism* Breast Neoplasms / pathology Cell Proliferation* / drug effects Dose-Response Relationship, Drug Estradiol / metabolism Estrogen Receptor alpha / drug effects Estrogen Receptor alpha / metabolism* Estrone / analogs & derivatives* Estrone / metabolism Estrone / pharmacology Female Gene Expression Regulation, Neoplastic HEK293 Cells Humans Ki-67 Antigen / metabolism MCF-7 Cells Organic Anion Transporters / genetics Organic Anion Transporters / metabolism* RNA, Messenger / metabolism Transcription, Genetic Transfection Up-Regulation
IF 2.772
Human and Animal Cells MCF7(RCB1904)