Functional analysis of SNPs variants of BCRP/ABCG2

Chihiro Kondo, Hiroshi Suzuki, Masaya Itoda, Shogo Ozawa, Jun Ichi Sawada, Daisuke Kobayashi, Ichiro Ieiri, Kazunori Mine, Kenji Ohtsubo, Yuichi Sugiyama

研究成果: ジャーナルへの寄稿記事

209 引用 (Scopus)

抄録

Purpose. The aim of the current study was to identify the effect of single nucleotide polymorphisms (SNPs) in breast cancer resistance protein (BCRP/ABCG2) on its localization, expression level, and transport activity. Methods. The cellular localization was identified using the wild type and seven different SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP) after transfection of their cDNAs in plasmid vector to LLC-PK1 cells. Their expression levels and transport activities were determined using the membrane vesicles from HEK293 cells infected with the recombinant adenoviruses containing these kinds of BCRP cDNAs. Results. Wild type and six different SNP variants of BCRP other than S441N BCRP were expressed on the apical membrane, whereas S441N BCRP showed intracellular localization. The expression levels of Q141K and S441N BCRP proteins were significantly lower compared with the wild type and the other five variants. Furthermore, the transport activity of E 1S, DHEAS, MTX, and PAH normalized by the expression level of BCRP protein was almost the same for the wild type, V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP. Conclusions. These results suggest that Q141K SNPs may associate with a lower expression level, and S441N SNPs may affect both the expression level and cellular localization. It is possible that subjects with these polymorphisms may have lower expression level of BCRP protein and, consequently, a reduced ability to export these substrates.

元の言語英語
ページ(範囲)1895-1903
ページ数9
ジャーナルPharmaceutical Research
21
発行部数10
DOI
出版物ステータス出版済み - 10 1 2004

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Functional analysis
Polymorphism
Single Nucleotide Polymorphism
Nucleotides
Complementary DNA
LLC-PK1 Cells
Proteins
Membranes
HEK293 Cells
Adenoviridae
Transfection
Polycyclic aromatic hydrocarbons
Plasmids
Breast Neoplasms
Substrates

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)

これを引用

Kondo, C., Suzuki, H., Itoda, M., Ozawa, S., Sawada, J. I., Kobayashi, D., ... Sugiyama, Y. (2004). Functional analysis of SNPs variants of BCRP/ABCG2. Pharmaceutical Research, 21(10), 1895-1903. https://doi.org/10.1023/B:PHAM.0000045245.21637.d4

Functional analysis of SNPs variants of BCRP/ABCG2. / Kondo, Chihiro; Suzuki, Hiroshi; Itoda, Masaya; Ozawa, Shogo; Sawada, Jun Ichi; Kobayashi, Daisuke; Ieiri, Ichiro; Mine, Kazunori; Ohtsubo, Kenji; Sugiyama, Yuichi.

:: Pharmaceutical Research, 巻 21, 番号 10, 01.10.2004, p. 1895-1903.

研究成果: ジャーナルへの寄稿記事

Kondo, C, Suzuki, H, Itoda, M, Ozawa, S, Sawada, JI, Kobayashi, D, Ieiri, I, Mine, K, Ohtsubo, K & Sugiyama, Y 2004, 'Functional analysis of SNPs variants of BCRP/ABCG2', Pharmaceutical Research, 巻. 21, 番号 10, pp. 1895-1903. https://doi.org/10.1023/B:PHAM.0000045245.21637.d4
Kondo, Chihiro ; Suzuki, Hiroshi ; Itoda, Masaya ; Ozawa, Shogo ; Sawada, Jun Ichi ; Kobayashi, Daisuke ; Ieiri, Ichiro ; Mine, Kazunori ; Ohtsubo, Kenji ; Sugiyama, Yuichi. / Functional analysis of SNPs variants of BCRP/ABCG2. :: Pharmaceutical Research. 2004 ; 巻 21, 番号 10. pp. 1895-1903.
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AU - Kondo, Chihiro

AU - Suzuki, Hiroshi

AU - Itoda, Masaya

AU - Ozawa, Shogo

AU - Sawada, Jun Ichi

AU - Kobayashi, Daisuke

AU - Ieiri, Ichiro

AU - Mine, Kazunori

AU - Ohtsubo, Kenji

AU - Sugiyama, Yuichi

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N2 - Purpose. The aim of the current study was to identify the effect of single nucleotide polymorphisms (SNPs) in breast cancer resistance protein (BCRP/ABCG2) on its localization, expression level, and transport activity. Methods. The cellular localization was identified using the wild type and seven different SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP) after transfection of their cDNAs in plasmid vector to LLC-PK1 cells. Their expression levels and transport activities were determined using the membrane vesicles from HEK293 cells infected with the recombinant adenoviruses containing these kinds of BCRP cDNAs. Results. Wild type and six different SNP variants of BCRP other than S441N BCRP were expressed on the apical membrane, whereas S441N BCRP showed intracellular localization. The expression levels of Q141K and S441N BCRP proteins were significantly lower compared with the wild type and the other five variants. Furthermore, the transport activity of E 1S, DHEAS, MTX, and PAH normalized by the expression level of BCRP protein was almost the same for the wild type, V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP. Conclusions. These results suggest that Q141K SNPs may associate with a lower expression level, and S441N SNPs may affect both the expression level and cellular localization. It is possible that subjects with these polymorphisms may have lower expression level of BCRP protein and, consequently, a reduced ability to export these substrates.

AB - Purpose. The aim of the current study was to identify the effect of single nucleotide polymorphisms (SNPs) in breast cancer resistance protein (BCRP/ABCG2) on its localization, expression level, and transport activity. Methods. The cellular localization was identified using the wild type and seven different SNP variants of BCRP (V12M, Q141K, A149P, R163K, Q166E, P269S, and S441N BCRP) after transfection of their cDNAs in plasmid vector to LLC-PK1 cells. Their expression levels and transport activities were determined using the membrane vesicles from HEK293 cells infected with the recombinant adenoviruses containing these kinds of BCRP cDNAs. Results. Wild type and six different SNP variants of BCRP other than S441N BCRP were expressed on the apical membrane, whereas S441N BCRP showed intracellular localization. The expression levels of Q141K and S441N BCRP proteins were significantly lower compared with the wild type and the other five variants. Furthermore, the transport activity of E 1S, DHEAS, MTX, and PAH normalized by the expression level of BCRP protein was almost the same for the wild type, V12M, Q141K, A149P, R163K, Q166E, and P269S BCRP. Conclusions. These results suggest that Q141K SNPs may associate with a lower expression level, and S441N SNPs may affect both the expression level and cellular localization. It is possible that subjects with these polymorphisms may have lower expression level of BCRP protein and, consequently, a reduced ability to export these substrates.

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