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

Down-Regulation of DNA Topoisomerase IIα Leads to Prolonged Cell Cycle Transit in G2 and Early M Phases and Increased Survival to Microtubule-Interacting Agents

Andrzej Skladanowski, Marie-George Côme, Michal Sabisz, Alexandre E. Escargueil and Annette K. Larsen
Molecular Pharmacology September 2005, 68 (3) 625-634; DOI: https://doi.org/10.1124/mol.105.013995
Andrzej Skladanowski
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Marie-George Côme
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Michal Sabisz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexandre E. Escargueil
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Annette K. Larsen
  • 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

Abstract

Microtubule binders are cell cycle-specific agents with preferential cytotoxicity toward mitotic cells. We have characterized vincristine-selected human leukemia cells to establish whether development of vincristine resistance was accompanied by changes in cell cycle kinetics and distribution. Our results indicate that vincristine resistance is accompanied by delayed G2 transit and prolonged early mitosis in both the absence and the presence of the microtubule binder nocodazole. The altered G2/M regulation is accompanied by resistance to short-term (12 h) but not continuous nocodazole exposure in agreement with the transient nature of the observed cell cycle alterations. Western blot analysis indicates that vincristine-selection is accompanied by down-regulation of topoisomerase IIα without detectable alterations of the other mitotic regulators studied, including Cdk1, p21, 14-3-3σ, and 14-3-3ϵ. This was associated with at least 7-fold less chromosome-associated topoisomerase IIα, decreased catalytic activity, and cross-resistance to topoisomerase II inhibitors. Characterization of isogenic cell lines expressing different levels of topoisomerase II proteins shows that cellular levels of topoisomerase IIα, but not the closely related topoisomerase IIβ, directly influence the cell cycle kinetics in G2 and early mitosis as well as the resistance to nocodazole. These results underline the importance of topoisomerase IIα in late G2 and early M phases and provide evidence for an as-yet-unsuspected interaction between topoisomerase II and microtubule-directed agents.

  • Received April 20, 2005.
  • Accepted June 7, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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: 68 (3)
Molecular Pharmacology
Vol. 68, Issue 3
1 Sep 2005
  • Table of Contents
  • About the Cover
  • Index by author
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.
Down-Regulation of DNA Topoisomerase IIα Leads to Prolonged Cell Cycle Transit in G2 and Early M Phases and Increased Survival to Microtubule-Interacting Agents
(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

Down-Regulation of DNA Topoisomerase IIα Leads to Prolonged Cell Cycle Transit in G2 and Early M Phases and Increased Survival to Microtubule-Interacting Agents

Andrzej Skladanowski, Marie-George Côme, Michal Sabisz, Alexandre E. Escargueil and Annette K. Larsen
Molecular Pharmacology September 1, 2005, 68 (3) 625-634; DOI: https://doi.org/10.1124/mol.105.013995

Citation Manager Formats

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

Share
Research ArticleArticle

Down-Regulation of DNA Topoisomerase IIα Leads to Prolonged Cell Cycle Transit in G2 and Early M Phases and Increased Survival to Microtubule-Interacting Agents

Andrzej Skladanowski, Marie-George Côme, Michal Sabisz, Alexandre E. Escargueil and Annette K. Larsen
Molecular Pharmacology September 1, 2005, 68 (3) 625-634; DOI: https://doi.org/10.1124/mol.105.013995
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • The binding site for KCI807 in the androgen receptor
  • Fatty acid amide hydrolase in cisplatin nephrotoxicity
  • eCB Signaling System in hiPSC-Derived Neuronal Cultures
Show more Article

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