Skip to main content
  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

  • Register
  • Log in
  • My Cart
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Journals
    • Blood Cancer Discovery
    • Cancer Discovery
    • Cancer Epidemiology, Biomarkers & Prevention
    • Cancer Immunology Research
    • Cancer Prevention Research
    • Cancer Research
    • Clinical Cancer Research
    • Molecular Cancer Research
    • Molecular Cancer Therapeutics

User menu

  • Register
  • Log in
  • My Cart

Search

  • Advanced search
Molecular Cancer Therapeutics
Molecular Cancer Therapeutics

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citation
    • Author/Keyword
  • News
    • Cancer Discovery News
Cancer Biology and Signal Transduction

Chemotherapy-Regulated microRNA-125–HER2 Pathway as a Novel Therapeutic Target for Trastuzumab-Mediated Cellular Cytotoxicity in Small Cell Lung Cancer

Shigehiro Yagishita, Yu Fujita, Satoru Kitazono, Ryo Ko, Yusuke Nakadate, Takeshi Sawada, Yuka Kitamura, Tatsu Shimoyama, Yoshiharu Maeda, Fumiyuki Takahashi, Kazuhisa Takahashi, Tomohide Tamura and Fumiaki Koizumi
Shigehiro Yagishita
Shien-Lab, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan. Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yu Fujita
Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tsukiji, Chuo-ku, Tokyo, Japan. Division of Respiratory Diseases, Department of Internal Medicine, Jikei University School of Medicine, Nishi-shinbashi, Minato-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Satoru Kitazono
Shien-Lab, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan. Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ryo Ko
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yusuke Nakadate
Shien-Lab, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Takeshi Sawada
Shien-Lab, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuka Kitamura
Shien-Lab, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tatsu Shimoyama
Department of Chemotherapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshiharu Maeda
Department of Chemotherapy, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fumiyuki Takahashi
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kazuhisa Takahashi
Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Hongo, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tomohide Tamura
Department of Thoracic Oncology, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Fumiaki Koizumi
Shien-Lab, National Cancer Center Hospital, Tsukiji, Chuo-ku, Tokyo, Japan. Department of Laboratory Medicine and Division of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Bunkyo-ku, Tokyo, Japan.
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: fkoizumi@cick.jp
DOI: 10.1158/1535-7163.MCT-14-0625 Published June 2015
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Small cell lung cancer (SCLC) accounts for 15% of all lung cancer cases and is a highly lethal disease. For the last several decades, the standard treatment for SCLC has been deadlocked, and new therapeutic strategies are urgently needed. HER2 is a member of the HER family and has been reported to be overexpressed in 30% of SCLC cases with poor prognosis. However, the clinical relevance of HER2-targeted therapy for SCLC remains unclear. Here, we first identify that cytotoxic drugs induce significant HER2 overexpression through microRNA-125a (miR-125a) and miR-125b downregulation, which in turn act as a novel therapeutic target for trastuzumab-mediated cellular cytotoxicity in SCLC. In this study, we showed that treatment of the HER2-positive SCLC cells, SBC-3 and SBC-5, with cytotoxic drugs induced a significant upregulation of HER2. Cisplatin (CDDP) treatment of SCLC cells resulted in a significant downregulation of miR-125a and miR-125b. We confirmed that miR-125a and miR-125b bound to the 3′-untranslated regions of HER2 mRNA, and that downregulation of miR-125a and miR-125b resulted in upregulation of HER2 in SCLC cells, suggesting a relationship between cytotoxic drug exposure and miR-125/HER2 dysregulation. Furthermore, using a calcein assay, we demonstrated a significantly enhanced cytotoxic effect of CDDP and trastuzumab that was mediated via antibody-dependent cellular cytotoxicity. Finally, we clearly demonstrated the enhanced antitumor effect of these agents in an orthotopic lung cancer model in vivo. Our results offer a novel therapeutic strategy for HER2-positive SCLCs by using trastuzumab combined with cytotoxic drugs. Mol Cancer Ther; 14(6); 1414–23. ©2015 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Molecular Cancer Therapeutics Online (http://mct.aacrjournals.org/).

  • Received July 28, 2014.
  • Revision received March 6, 2015.
  • Accepted March 10, 2015.
  • ©2015 American Association for Cancer Research.
View Full Text
PreviousNext
Back to top
Molecular Cancer Therapeutics: 14 (6)
June 2015
Volume 14, Issue 6
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover

Sign up for alerts

View this article with LENS

Open full page PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Molecular Cancer 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.
Chemotherapy-Regulated microRNA-125–HER2 Pathway as a Novel Therapeutic Target for Trastuzumab-Mediated Cellular Cytotoxicity in Small Cell Lung Cancer
(Your Name) has forwarded a page to you from Molecular Cancer Therapeutics
(Your Name) thought you would be interested in this article in Molecular Cancer Therapeutics.
Citation Tools
Chemotherapy-Regulated microRNA-125–HER2 Pathway as a Novel Therapeutic Target for Trastuzumab-Mediated Cellular Cytotoxicity in Small Cell Lung Cancer
Shigehiro Yagishita, Yu Fujita, Satoru Kitazono, Ryo Ko, Yusuke Nakadate, Takeshi Sawada, Yuka Kitamura, Tatsu Shimoyama, Yoshiharu Maeda, Fumiyuki Takahashi, Kazuhisa Takahashi, Tomohide Tamura and Fumiaki Koizumi
Mol Cancer Ther June 1 2015 (14) (6) 1414-1423; DOI: 10.1158/1535-7163.MCT-14-0625

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Chemotherapy-Regulated microRNA-125–HER2 Pathway as a Novel Therapeutic Target for Trastuzumab-Mediated Cellular Cytotoxicity in Small Cell Lung Cancer
Shigehiro Yagishita, Yu Fujita, Satoru Kitazono, Ryo Ko, Yusuke Nakadate, Takeshi Sawada, Yuka Kitamura, Tatsu Shimoyama, Yoshiharu Maeda, Fumiyuki Takahashi, Kazuhisa Takahashi, Tomohide Tamura and Fumiaki Koizumi
Mol Cancer Ther June 1 2015 (14) (6) 1414-1423; DOI: 10.1158/1535-7163.MCT-14-0625
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike 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
    • Disclosure of Potential Conflicts of Interest
    • Authors' Contributions
    • Grant Support
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Proinflammatory Cytokines and Drug Resistance
  • Decitabine and the MUC1-C Inhibitor Synergize in CTCL
  • Targeting Androgen Receptor Interactions with Chromatin
Show more Cancer Biology and Signal Transduction
  • Home
  • Alerts
  • Feedback
  • Privacy Policy
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

  • Online First
  • Current Issue
  • Past Issues
  • Meeting Abstracts

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About MCT

  • About the Journal
  • Editorial Board
  • Permissions
  • Submit a Manuscript
AACR logo

Copyright © 2019 by the American Association for Cancer Research.

Molecular Cancer Therapeutics
eISSN: 1538-8514
ISSN: 1535-7163

Advertisement