Epigenetic Regulation of Organic Anion Transporting Polypeptide 1B3 in Cancer Cell Lines
| Autor: | Sotaro Naoi, Hiroyuki Kusuhara, Yuri Tsuruya, Sho Nishida, Yuichi Sugiyama, Ryota Kikuchi, Satoki Imai |
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| Rok vydání: | 2013 |
| Předmět: |
Organic anion transporter 1
Pharmaceutical Science Organic Anion Transporters Sodium-Independent Biology Cell Line Epigenesis Genetic Solute Carrier Organic Anion Transporter Family Member 1B3 Cell Line Tumor Neoplasms Humans Gene silencing Pharmacology (medical) RNA Messenger Epigenetics Pharmacology Regulation of gene expression Organic Chemistry DNA Methylation Molecular biology Cell biology DNA-Binding Proteins Gene Expression Regulation Neoplastic Organic anion-transporting polypeptide Cell culture Cancer cell DNA methylation biology.protein Molecular Medicine RNA Interference Biotechnology |
| Zdroj: | Pharmaceutical Research. 30:2880-2890 |
| ISSN: | 1573-904X 0724-8741 |
| Popis: | The expression of a multispecific organic anion transporter, OATP1B3/SLCO1B3, is associated with clinical prognosis and survival of cancer cells. The aims of present study were to investigate the involvement of epigenetic regulation in mRNA expression of a cancer-type variant of OATP1B3 (Ct-OATP1B3) in cancer cell lines. The membrane localization and transport functions of Ct-OATP1B3 were investigated in HEK293 cells transiently expressing Ct-OATP1B3. DNA methylation profiles around the transcriptional start site of Ct-OATP1B3 in cancer cell lines were determined. The effects of a DNA methyltransferase inhibitor and siRNA knockdown of methyl-DNA binding proteins (MBDs) on the expression of Ct-OATP1B3 mRNA were investigated. 5′-RACE identified the TSS of Ct-OATP1B3 in PK-8 cells. Ct-OATP1B3 was localized on the plasma membrane, and showed the transport activities of E217βG, fluvastatin, rifampicin, and Gd-EOB-DTPA. The CpG dinucleotides were hypomethylated in Ct-OATP1B3-positive cell lines (DLD-1, TFK-1, PK-8, and PK-45P) but were hypermethylated in Ct-OATP1B3-negative cell lines (HepG2 and Caco-2). Treatment with a DNA methyltransferase inhibitor and siRNA knockdown of MBD2 significantly increased the expression of Ct-OATP1B3 mRNA in HepG2 and Caco-2. Ct-OATP1B3 is capable of transporting its substrates into cancer cells. Its mRNA expression is regulated by DNA methylation-dependent gene silencing involving MBD2. |
| Databáze: | OpenAIRE |
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