Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

FUNCTIONAL ASSESSMENT OF ABCG2 (BCRP) GENE POLYMORPHISMS TO PROTEIN EXPRESSION IN HUMAN PLACENTA

Daisuke Kobayashi, Ichiro Ieiri, Takeshi Hirota, Hiroshi Takane, Shinji Maegawa, Junzo Kigawa, Hiroshi Suzuki, Eiji Nanba, Mitsuo Oshimura, Naoki Terakawa, Kenji Otsubo, Kazunori Mine and Yuichi Sugiyama
Drug Metabolism and Disposition January 2005, 33 (1) 94-101; DOI: https://doi.org/10.1124/dmd.104.001628
Daisuke Kobayashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ichiro Ieiri
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeshi Hirota
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Takane
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinji Maegawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Junzo Kigawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hiroshi Suzuki
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Eiji Nanba
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mitsuo Oshimura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Naoki Terakawa
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kenji Otsubo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazunori Mine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuichi Sugiyama
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

The aim of the present study was to assess the contribution of polymorphisms in the breast cancer resistance protein/ATP-binding cassette transporter G2 (BCRP/ABCG2) gene to the placental expression from a new perspective, allelic imbalance. Polymorphisms were screened by polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis followed by sequencing with DNA extracted from 100 placentas. To examine whether polymorphisms of the BCRP gene correlate with the placental BCRP expression, we determined mRNA and protein levels by quantitative real-time PCR and Western blotting, respectively. In placentas, G34A (Val12Met) and C421A (Gln141Lys) were frequently observed (18-36%), but C376T, which creates a stop codon (Gln126 stop codon), was found with an allelic frequency of 1%. The mean of the BCRP protein level was significantly lower (p < 0.05) in homozygotes for the A421 allele than in those for the C421 allele, and heterozygotes had an intermediate value. To evaluate whether the C421A polymorphism acts as a cis-element in BCRP transcription, allelic imbalance was determined using informative lymphoblasts and 56 samples of placental cDNA. In most of the placental samples we tested, the difference in expression levels between the two alleles was small, and only two samples indicated a monoallelic expression (i.e., preferential expression of one allele). These results suggest that 1) the predominant allelic expression pattern of BCRP in placental samples is biallelic, and 2) the mutation C421A is not a genetic variant acting in cis, but is considered to influence the translation efficiency.

Footnotes

  • This study is supported by Health and Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare, Tokyo, Japan.

  • doi:10.1124/dmd.104.001628.

  • ABBREVIATIONS: BCRP, breast cancer resistance protein; ABC, ATP-binding cassette transporter; GF120918, N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide; RT, reverse transcriptase; PCR, polymerase chain reaction; SSCP, single-strand conformation polymorphism; bp, pase pair(s); SNP, single-nucleotide polymorphism; PCR-RFLP, PCR-restriction fragment length polymorphism; ALP, alkaline phosphatase; TPBS, 1× phosphate-buffered saline, 0.1% Tween 20; EB, Epstein-Barr.

    • Received July 25, 2004.
    • Accepted October 7, 2004.
  • The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 33 (1)
Drug Metabolism and Disposition
Vol. 33, Issue 1
1 Jan 2005
  • Table of Contents
  • About the Cover
  • Index by author
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
FUNCTIONAL ASSESSMENT OF ABCG2 (BCRP) GENE POLYMORPHISMS TO PROTEIN EXPRESSION IN HUMAN PLACENTA
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

FUNCTIONAL ASSESSMENT OF ABCG2 (BCRP) GENE POLYMORPHISMS TO PROTEIN EXPRESSION IN HUMAN PLACENTA

Daisuke Kobayashi, Ichiro Ieiri, Takeshi Hirota, Hiroshi Takane, Shinji Maegawa, Junzo Kigawa, Hiroshi Suzuki, Eiji Nanba, Mitsuo Oshimura, Naoki Terakawa, Kenji Otsubo, Kazunori Mine and Yuichi Sugiyama
Drug Metabolism and Disposition January 1, 2005, 33 (1) 94-101; DOI: https://doi.org/10.1124/dmd.104.001628

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

FUNCTIONAL ASSESSMENT OF ABCG2 (BCRP) GENE POLYMORPHISMS TO PROTEIN EXPRESSION IN HUMAN PLACENTA

Daisuke Kobayashi, Ichiro Ieiri, Takeshi Hirota, Hiroshi Takane, Shinji Maegawa, Junzo Kigawa, Hiroshi Suzuki, Eiji Nanba, Mitsuo Oshimura, Naoki Terakawa, Kenji Otsubo, Kazunori Mine and Yuichi Sugiyama
Drug Metabolism and Disposition January 1, 2005, 33 (1) 94-101; DOI: https://doi.org/10.1124/dmd.104.001628
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Appendix
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Series-Compartment Models of Hepatic Elimination
  • Warfarin PBPK Model with TMDD Mechanism
  • Identification of payload-containing catabolites of ADCs
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics