| RRC ID |
61893
|
| 著者 |
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.
|
| タイトル |
Organic anion transporting polypeptide 2B1 expression correlates with uptake of estrone-3-sulfate and cell proliferation in estrogen receptor-positive breast cancer cells.
|
| ジャーナル |
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.
|
| 巻・号 |
30(2)
|
| ページ |
133-41
|
| 公開日 |
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
|
| リソース情報 |
| ヒト・動物細胞 |
MCF7(RCB1904) |
