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
Molecular Pharmacology
  • 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
Molecular Pharmacology

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 molpharm on Facebook
  • Follow molpharm on Twitter
  • Follow molpharm on LinkedIn
Research ArticleArticle

Aryl Hydrocarbon Receptor Is a Transcriptional Activator of the Human Breast Cancer Resistance Protein (BCRP/ABCG2)

Kah Poh Tan, Bernice Wang, Mingdong Yang, Paul C. Boutros, Jane MacAulay, Haibo Xu, Andrew I. Chuang, Kazuhiro Kosuge, Mika Yamamoto, Shinichiro Takahashi, Alex M. L. Wu, Douglas D. Ross, Patricia A. Harper and Shinya Ito
Molecular Pharmacology August 2010, 78 (2) 175-185; DOI: https://doi.org/10.1124/mol.110.065078
Kah Poh Tan
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernice Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mingdong Yang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul C. Boutros
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jane MacAulay
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haibo Xu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Andrew I. Chuang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhiro Kosuge
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mika Yamamoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinichiro Takahashi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alex M. L. Wu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas D. Ross
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patricia A. Harper
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinya Ito
  • 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

Breast cancer resistance protein (BCRP/ABCG2) is a membrane-bound efflux transporter important in cellular detoxification and multidrug resistance. Some aryl hydrocarbon receptor (AHR) agonists were reported to induce BCRP expression in human colon carcinoma cells. However, a direct involvement of AHR transcriptional regulation remains unexplored. In this study, we show that BCRP induction by AHR ligands occurs in human intestinal, liver, and mammary carcinoma cells and in primary colonocytes and hepatocytes. Increased BCRP transporter activity consistent with gene induction was also evident in the Caco2 subclone C2bbe1 cells. Using RNA interference and ectopic expression techniques to manipulate cellular AHR status, we confirmed AHR dependence of ABCG2 gene regulation. By gene promoter analysis, chromatin immunoprecipitation, and electrophoretic mobility shift assays, an active, proximal dioxin-response element at −194/−190 base pairs upstream of the transcription start site of the human ABCG2 gene was identified. Despite a common observation in human-derived cells, our in vitro and in vivo studies supported by phylogenetic footprinting analysis did not find that mouse Abcg2 is subject to AHR regulation. We conclude that AHR is a direct transcriptional regulator of human BCRP and provide an unprecedented role of AHR in cellular adaptive response and cytoprotection by up-regulating an important ATP-binding cassette efflux transporter.

Footnotes

  • ↵Embedded Image The online version of this article (available at http://molpharm.aspetjournals.org) contains supplemental material.

  • This work was supported by the Canadian Institute of Health Research [Grant MT13747] and the VA Merit Review.

  • Article, publication date, and citation information can be found at http://molpharm.aspetjournals.org.

    doi:10.1124/mol.110.065078.

  • ABBREVIATIONS:

    BCRP
    breast cancer resistance protein
    ABC
    ATP-binding cassette
    ABCG2
    ATP-binding cassette G2 protein
    AHR
    aryl hydrocarbon receptor
    ChIP
    chromatin immunoprecipitation
    DBA
    dimethyl-benzo(a)pyrene
    DMF
    3,4-dimethoxyflavone
    DMSO
    dimethyl sulfoxide
    DRE
    dioxin response element
    EMSA
    electrophoretic mobility shift assay
    ERα
    estrogen receptor-α
    FTC
    fumitremorgin C
    HIF-1α
    hypoxia-inducible factor 1α
    3MC
    3-methylcholanthrene
    Nrf2
    nuclear factor (erythroid 2-like) factor 2
    PgR
    progesterone receptor
    PCR
    polymerase chain reaction
    siRNA
    small interfering RNA
    TCDD
    2,3,7,8-tetrachlorodibenzo-p-dioxin
    bp
    base pair
    RT-PCR
    reverse-transcriptase polymerase chain reaction
    GAPDH
    glyceraldehyde-3-phosphate dehydrogenase
    SV40
    simian virus 40
    ANOVA
    analysis of variance
    ERE
    estrogen response element
    HRE
    hypoxia response element
    ARNT
    aryl hydrocarbon receptor nuclear translocator
    PD98059
    2′-amino-3′-methoxyflavone
    SN-38
    7-ethyl-10-hydroxycamptothecin.

  • Received March 25, 2010.
  • Accepted May 5, 2010.
  • U.S. Government work not protected by U.S. copyright
View Full Text

MolPharm 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

Molecular Pharmacology: 78 (2)
Molecular Pharmacology
Vol. 78, Issue 2
1 Aug 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • 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 Molecular Pharmacology 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.
Aryl Hydrocarbon Receptor Is a Transcriptional Activator of the Human Breast Cancer Resistance Protein (BCRP/ABCG2)
(Your Name) has forwarded a page to you from Molecular Pharmacology
(Your Name) thought you would be interested in this article in Molecular Pharmacology.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Aryl Hydrocarbon Receptor Is a Transcriptional Activator of the Human Breast Cancer Resistance Protein (BCRP/ABCG2)

Kah Poh Tan, Bernice Wang, Mingdong Yang, Paul C. Boutros, Jane MacAulay, Haibo Xu, Andrew I. Chuang, Kazuhiro Kosuge, Mika Yamamoto, Shinichiro Takahashi, Alex M. L. Wu, Douglas D. Ross, Patricia A. Harper and Shinya Ito
Molecular Pharmacology August 1, 2010, 78 (2) 175-185; DOI: https://doi.org/10.1124/mol.110.065078

Citation Manager Formats

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

Share
Research ArticleArticle

Aryl Hydrocarbon Receptor Is a Transcriptional Activator of the Human Breast Cancer Resistance Protein (BCRP/ABCG2)

Kah Poh Tan, Bernice Wang, Mingdong Yang, Paul C. Boutros, Jane MacAulay, Haibo Xu, Andrew I. Chuang, Kazuhiro Kosuge, Mika Yamamoto, Shinichiro Takahashi, Alex M. L. Wu, Douglas D. Ross, Patricia A. Harper and Shinya Ito
Molecular Pharmacology August 1, 2010, 78 (2) 175-185; DOI: https://doi.org/10.1124/mol.110.065078
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

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

Related Articles

Cited By...

More in this TOC Section

  • Fatty Acid Amide Hydrolase in Cisplatin Nephrotoxicity
  • Use-Dependent Relief of A-887826 Inhibition
  • Benzbromarone Relaxes Airway Smooth Muscle via BK Activation
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 Molecular Pharmacology
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Drug Metabolism and Disposition
  • Journal of Pharmacology and Experimental Therapeutics
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0111 (Online)

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