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

Induction of Multidrug Resistance Transporter ABCG2 by Prolactin in Human Breast Cancer Cells

Alex Man Lai Wu, Pooja Dalvi, Xiaoli Lu, Mingdong Yang, David S. Riddick, Jason Matthews, Charles V. Clevenger, Douglas D. Ross, Patricia A. Harper and Shinya Ito
Molecular Pharmacology February 2013, 83 (2) 377-388; DOI: https://doi.org/10.1124/mol.112.082362
Alex Man Lai Wu
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pooja Dalvi
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Xiaoli Lu
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mingdong Yang
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
David S. Riddick
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jason Matthews
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Charles V. Clevenger
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Douglas D. Ross
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patricia A. Harper
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Shinya Ito
Program in Physiology and Experimental Medicine (A.M.L.W., P.D., X.L., M.Y., S.I.), Program in Developmental and Stem Cell Biology (P.A.H.), Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada; Departments of Pediatrics (S.I.), and Pharmacology & Toxicology (A.M.L.W., D.S.R., J.M., P.A.H., S.I.), University of Toronto, Toronto, Ontario, Canada; Department of Pathology (C.V.C.), Feinberg School of Medicine, Northwestern University, Chicago, Illinois; Program in Experimental Therapeutics, University of Maryland Greenebaum Cancer Center, and the Baltimore Veterans Affairs Medical Center, Baltimore, Maryland (D.D.R.).
  • 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

The multidrug transporter, breast cancer resistance protein, ABCG2, is up-regulated in certain chemoresistant cancer cells and in the mammary gland during lactation. We investigated the role of the lactogenic hormone prolactin (PRL) in the regulation of ABCG2. PRL dose-dependently induced ABCG2 expression in T-47D human breast cancer cells. This induction was significantly reduced by short-interfering RNA–mediated knockdown of Janus kinase 2 (JAK2). Knockdown or pharmacologic inhibition of the down-stream signal transducer and activator of transcription-5 (STAT5) also blunted the induction of ABCG2 by PRL, suggesting a role for the JAK2/STAT5 pathway in PRL-induced ABCG2 expression. Corroborating these findings, we observed PRL-stimulated STAT5 recruitment to a region containing a putative γ-interferon activation sequence (GAS) element at −434 base pairs upstream of the ABCG2 transcription start site. Introduction of a single mutation to the −434 GAS element significantly attenuated PRL-stimulated activity of a luciferase reporter driven by the ABCG2 gene promoter and 5′-flanking region containing the −434 GAS motif. In addition, this GAS element showed strong copy number dependency in its response to PRL treatment. Interestingly, inhibitors against the mitogen-activated protein kinase and phosphoinositide-3-kinase signaling pathways significantly decreased the induction of ABCG2 by PRL without altering STAT5 recruitment to the GAS element. We conclude that the JAK2/STAT5 pathway is required but not sufficient for the induction of ABCG2 by PRL.

Footnotes

  • This work was mainly supported by the Canadian Institutes of Health Research [Grants MT13747 and MOP-93759] and Frederick Banting and Charles Best Canada Graduate Scholarship, with additional support provided in part by University of Toronto Fellowship, Avon Foundation, and by a Merit Review grant from the US Department of Veterans Affairs.

  • ↵dx.doi.org/10.1124/mol.112.082362.

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

  • Received September 12, 2012.
  • Accepted November 13, 2012.
  • 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: 83 (2)
Molecular Pharmacology
Vol. 83, Issue 2
1 Feb 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 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.
Induction of Multidrug Resistance Transporter ABCG2 by Prolactin in Human Breast Cancer Cells
(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

Prolactin induces multidrug resistance transporter ABCG2

Alex Man Lai Wu, Pooja Dalvi, Xiaoli Lu, Mingdong Yang, David S. Riddick, Jason Matthews, Charles V. Clevenger, Douglas D. Ross, Patricia A. Harper and Shinya Ito
Molecular Pharmacology February 1, 2013, 83 (2) 377-388; DOI: https://doi.org/10.1124/mol.112.082362

Citation Manager Formats

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

Share
Research ArticleArticle

Prolactin induces multidrug resistance transporter ABCG2

Alex Man Lai Wu, Pooja Dalvi, Xiaoli Lu, Mingdong Yang, David S. Riddick, Jason Matthews, Charles V. Clevenger, Douglas D. Ross, Patricia A. Harper and Shinya Ito
Molecular Pharmacology February 1, 2013, 83 (2) 377-388; DOI: https://doi.org/10.1124/mol.112.082362
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

  • Therapeutic Effects of FGF23 Antagonists in Hyp Mice
  • TRPV3 and TRPV4 Channels Coassemble into Heterotetramers
  • Secretin Amino-Terminal Structure-Activity Relationships and Complementary Mutagenesis at the Site of Docking to the Secretin Receptor
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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics