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Characterization of Human OATP2B1 (SLCO2B1) Gene Promoter Regulation

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Purpose

We investigated transcriptional regulation of organic anion transporter OATP2B1 (SLCO2B1) that is expressed in multiple tissues such as liver, small intestine, and others and compared it with that of liver-specific OATPs.

Methods

The promoter activity was examined by luciferase assay. Specific bindings of transcription factors to the promoter region were examined by gel mobility shift assay using native and mutated nucleotides of the promoter region of OATP2B1.

Results

Deletion–mutation study of the promoter region of OATP2B1 showed that the −59 region that included the Sp1 binding site had basal promoter activity, whereas promoter activities of the further upper region were different between intestine-derived Caco-2 cells and liver-derived HepG2 cells. The association of Sp1 to the promoter region was confirmed by gel shift assay and overexpression of Sp1 in cultured cells. Although the promoter of OATP2B1 has a putative HNF1α binding site, overexpression of HNF1α did not induce the expression of OATP2B1.

Conclusion

Sp1, a transcription factor, was required for constitutive expression of OATP2B1 in liver and small intestine, whereas HNF1α, which is involved in the expression of liver-specific OATPs, did not seem to play a role in OATP2B1 expression. Accordingly, it was suggested that the tissue expression profile of OATP2B1 was different from that of other liver-specific OATPs.

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Abbreviations

DMEM:

Dulbecco's modified Eagle's medium

FBS:

fetal bovine serum

MEM:

Eagle's minimum essential medium

OATP:

organic anion-transporting peptide

PBS:

phosphate-buffered saline

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Acknowledgment

This investigation was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

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Authors and Affiliations

  1. Department of Molecular Biopharmaceutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamasaki, Noda, Chiba, 278-8510, Japan

    Tomoji Maeda, Masamichi Hirayama, Ryunosuke Higashi, Masanobu Sato & Ikumi Tamai

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  1. Tomoji Maeda
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  2. Masamichi Hirayama
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  3. Ryunosuke Higashi
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  4. Masanobu Sato
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  5. Ikumi Tamai
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Correspondence to Ikumi Tamai.

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Maeda, T., Hirayama, M., Higashi, R. et al. Characterization of Human OATP2B1 (SLCO2B1) Gene Promoter Regulation. Pharm Res 23, 513–520 (2006). https://doi.org/10.1007/s11095-006-9572-6

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  • DOI: https://doi.org/10.1007/s11095-006-9572-6

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