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

Overlapping Substrate and Inhibitor Specificity of Human and Murine ABCG2

Joshua Bakhsheshian, Matthew D. Hall, Robert W. Robey, Michelle A. Herrmann, Jin-Qiu Chen, Susan E. Bates and Michael M. Gottesman
Drug Metabolism and Disposition October 2013, 41 (10) 1805-1812; DOI: https://doi.org/10.1124/dmd.113.053140
Joshua Bakhsheshian
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew D. Hall
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Robert W. Robey
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michelle A. Herrmann
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jin-Qiu Chen
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Susan E. Bates
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michael M. Gottesman
Laboratory of Cell Biology (J.B., M.D.H., M.M.G.), Cancer Therapeutics Branch (R.W.R., S.E.B.), Collaborative Protein Technology Resource (M.A.H., J.-Q.C.), Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
  • 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 + SI
  • PDF
Loading

Abstract

ABCG2 (also known as breast cancer resistance protein) is an ATP-binding cassette (ABC) transporter localized to the plasma membrane where it mediates the efflux of xenobiotics, including potential therapeutics. Studies investigating Abcg2 function at the blood-brain barrier in mouse models are often compared with human ABCG2 function. It is critical to understand the nature of species differences between mouse and human ABCG2, since extrapolations are made from murine data to humans. Two independent drug-selected cell line pairs expressing human or mouse ABCG2 were compared for efflux of fluorescent substrates using flow cytometry. To this end, we developed and characterized a new mouse Abcg2-expressing subline that demonstrated efflux of known fluorescent ABCG2 substrates and increased resistance to mitoxantrone, which is reduced in the presence of the ABCG2 inhibitor Ko143. Our results indicate that the substrate specificity of human and mouse ABCG2 is very similar. We identified a new human and mouse ABCG2 substrate, a porphyrin analog, purpurin-18 (Pp-18), which is not a substrate for P-glycoprotein or multidrug resistance protein 1. The ability of inhibitors to block efflux activity of ABCG2 was assessed using Pp-18. Inhibitors also demonstrated similar effects on human and mouse ABCG2. Chrysin, benzoflavone, and cyclosporin A inhibited Pp-18 efflux in both human and mouse ABCG2. The similarity of the substrate and inhibitor specificity of human and mouse ABCG2 supports interpretation of mouse models in understanding the clinical, pharmacological, and physiologic roles of ABCG2.

Footnotes

    • Received May 30, 2013.
    • Accepted July 18, 2013.
  • This research was supported by the Intramural Research Program of the National Institutes of Health [National Cancer Institute]. J.B. is a National Institutes of Health Medical Research Scholar. The authors declare no conflicts of interest.

  • dx.doi.org/10.1124/dmd.113.053140.

  • ↵Embedded ImageThis article has supplemental material available at dmd.aspetjournals.org.

  • U.S. Government work not protected by U.S. copyright
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: 41 (10)
Drug Metabolism and Disposition
Vol. 41, Issue 10
1 Oct 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
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.
Overlapping Substrate and Inhibitor Specificity of Human and Murine ABCG2
(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 Comparison of Human and Murine ABCG2

Joshua Bakhsheshian, Matthew D. Hall, Robert W. Robey, Michelle A. Herrmann, Jin-Qiu Chen, Susan E. Bates and Michael M. Gottesman
Drug Metabolism and Disposition October 1, 2013, 41 (10) 1805-1812; DOI: https://doi.org/10.1124/dmd.113.053140

Citation Manager Formats

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

Share
Research ArticleArticle

Functional Comparison of Human and Murine ABCG2

Joshua Bakhsheshian, Matthew D. Hall, Robert W. Robey, Michelle A. Herrmann, Jin-Qiu Chen, Susan E. Bates and Michael M. Gottesman
Drug Metabolism and Disposition October 1, 2013, 41 (10) 1805-1812; DOI: https://doi.org/10.1124/dmd.113.053140
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
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF + SI
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Identification of payload-containing catabolites of ADCs
  • PK Interactions of Licorice with Cytochrome P450s
  • Biotransformation of Trastuzumab and Pertuzumab
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