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
Journal of Pharmacology and Experimental Therapeutics
  • 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
Journal of Pharmacology and Experimental Therapeutics

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 jpet on Facebook
  • Follow jpet on Twitter
  • Follow jpet on LinkedIn
Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Induction of Epithelial-Mesenchymal Transition via Activation of Epidermal Growth Factor Receptor Contributes to Sunitinib Resistance in Human Renal Cell Carcinoma Cell Lines

Atsushi Mizumoto, Kazuhiro Yamamoto, Yuko Nakayama, Kohji Takara, Tsutomu Nakagawa, Takeshi Hirano and Midori Hirai
Journal of Pharmacology and Experimental Therapeutics November 2015, 355 (2) 152-158; DOI: https://doi.org/10.1124/jpet.115.226639
Atsushi Mizumoto
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhiro Yamamoto
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuko Nakayama
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kohji Takara
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tsutomu Nakagawa
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeshi Hirano
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Midori Hirai
Division of Pharmacokinetics, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Hyogo, Japan (A.M., T.N., T.H., M.H.); Department of Pharmacy, Kobe University Hospital, Hyogo, Japan (K.Y., T.N., T.H., M.H.); and Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Hyogo, Japan (Y.N., K.T.)
  • 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

Visual Overview

Figure
  • Download figure
  • Open in new tab
  • Download powerpoint

Abstract

Sunitinib is widely used for treating renal cell carcinoma (RCC). However, some patients do not respond to treatment with this drug. We aimed to study the association between sunitinib sensitivity and epithelial-mesenchymal transition (EMT) regulation via epidermal growth factor receptor (EGFR) signaling, which is a mechanism of resistance to anticancer drugs. Three RCC cell lines (786-O, ACHN, and Caki-1) were used, and then we evaluated cell viability, EMT regulatory proteins, and signal transduction with sunitinib treatment. Cell viability of 786-O cells was maintained after treatment with sunitinib. After treatment with sunitinib, EGFR phosphorylation increased in 786-O cells, resulting in an increase in the phosphorylation of extracellular signal-regulated kinase, nuclear translocation of β-catenin, and expression of mesenchymal markers. These results suggest that sunitinib induced EMT via activation of EGFR in 786-O cells, but not in ACHN and Caki-1 cells. Caki-1/SN cells, a resistant cell line generated by continuous exposure to sunitinib, displayed increased phosphorylation of EGFR. Cell viability in the presence of sunitinib was decreased by erlotinib, as the selective inhibitor of EGFR, treatment in 786-O and Caki-1/SN cells. Similarly, erlotinib suppressed sunitinib-induced EGFR activation and upregulated mesenchymal markers. Thus, we postulate that resistance to sunitinib in RCC may be associated with EMT caused by activation of EGFR.

Footnotes

    • Received June 9, 2015.
    • Accepted August 21, 2015.
  • This research was supported by the Kobe University Research Fund of 2013–2014.

  • dx.doi.org/10.1124/jpet.115.226639.

  • Copyright © 2015 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

JPET 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

Journal of Pharmacology and Experimental Therapeutics: 355 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 355, Issue 2
1 Nov 2015
  • 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 Journal of Pharmacology and Experimental Therapeutics 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 Epithelial-Mesenchymal Transition via Activation of Epidermal Growth Factor Receptor Contributes to Sunitinib Resistance in Human Renal Cell Carcinoma Cell Lines
(Your Name) has forwarded a page to you from Journal of Pharmacology and Experimental Therapeutics
(Your Name) thought you would be interested in this article in Journal of Pharmacology and Experimental Therapeutics.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Sunitinib Induces EMT via EGFR Activation in 786-O Cells

Atsushi Mizumoto, Kazuhiro Yamamoto, Yuko Nakayama, Kohji Takara, Tsutomu Nakagawa, Takeshi Hirano and Midori Hirai
Journal of Pharmacology and Experimental Therapeutics November 1, 2015, 355 (2) 152-158; DOI: https://doi.org/10.1124/jpet.115.226639

Citation Manager Formats

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

Share
Research ArticleChemotherapy, Antibiotics, and Gene Therapy

Sunitinib Induces EMT via EGFR Activation in 786-O Cells

Atsushi Mizumoto, Kazuhiro Yamamoto, Yuko Nakayama, Kohji Takara, Tsutomu Nakagawa, Takeshi Hirano and Midori Hirai
Journal of Pharmacology and Experimental Therapeutics November 1, 2015, 355 (2) 152-158; DOI: https://doi.org/10.1124/jpet.115.226639
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Visual Overview
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Targeting LGR5-Positive Cells in Ovarian Cancer
  • Ocular Palonosetron for Prevention of Nausea and Vomiting
  • PTP4A3 and Ovarian Cancer
Show more Chemotherapy, Antibiotics, and Gene Therapy

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 JPET
  • 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
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-0103 (Online)

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