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

AACR logo

  • 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
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

  • 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
  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Meeting Abstracts
    • Collections
      • COVID-19 & Cancer Resource Center
      • Focus on Radiation Oncology
      • Novel Combinations
      • Reviews
      • Editors' Picks
      • "Best of" Collection
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • Editors' Picks
    • OnlineFirst
    • Citation
    • Author/Keyword
    • RSS Feeds
    • My Alert Summary & Preferences
  • News
    • Cancer Discovery News
  • COVID-19
  • Webinars
  • Search More

    Advanced Search

Article

Conservation of the Class I β-Tubulin Gene in Human Populations and Lack of Mutations in Lung Cancers and Paclitaxel-resistant Ovarian Cancers1

Sanja Šale, Raphael Sung, Peidong Shen, Kristine Yu, Yan Wang, George E. Duran, Jong-Hyeok Kim, Tito Fojo, Peter J. Oefner and Branimir I. Sikic
Sanja Šale
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Raphael Sung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peidong Shen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Kristine Yu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yan Wang
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
George E. Duran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jong-Hyeok Kim
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tito Fojo
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Peter J. Oefner
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Branimir I. Sikic
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published January 2002
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

The goal of this study was to determine the prevalence of sequence variants in the class I β-tubulin (clone m40) gene and their occurrence in human tumors and cancer cell lines. DNA was isolated from 93 control individuals representing a wide variety of ethnicities, 49 paclitaxel-naive specimens (16 ovarian cancers, 17 non-small cell lung cancers, and 16 ovarian cancer cell lines), and 30 paclitaxel-resistant specimens (9 ovarian cancers, 9 ovarian cancer cell lines, and 12 ovarian cancer xenografts in nude mice). Denaturing high-performance liquid chromatography and direct sequence analysis detected two silent polymorphisms in exon 4, Leu217Leu (CTG/CTA) and Gly400Gly (GGC/GGT), with minor allele frequencies of 17 and 0.5%, respectively. Five nucleotide substitutions and one single-base deletion were detected in introns 1, 2, and 3 and in the 3′ untranslated region. Analysis of 49 paclitaxel-naive and 30 paclitaxel-resistant specimens revealed no additional polymorphisms in the coding region. In addition, no amino acid replacements were found in chimpanzee, gorilla, and orangutan in comparison to human. Our data demonstrate a very high degree of sequence conservation in class I β-tubulin, suggesting that all residues are important in tubulin structure and function. Individual variation in response to treatment with paclitaxel is not likely to be caused by genetic variations in the β-tubulin drug target. Moreover, acquired mutations in class I β-tubulin are unlikely to be a clinically relevant cause of drug resistance.

Footnotes

  • ↵1 This work was supported by NIH Grants R01 CA 68217 (to B. I. S.) and R01 HG01932 (to P. J. O.), California Cancer Research Program Grant 99-00561V-10091 (to B. I. S.), and the Margaret Fagin and Beatrice Quackenbush Ovarian Cancer Research Funds.

  • ↵2 To whom requests for reprints should be addressed, at Stanford University School of Medicine, Oncology Division, 269 Campus Drive, CCSR-1105, Stanford, CA 94305-5151. Phone: (650) 725-6427; Fax: (650) 736-1454; E-mail: brandy{at}stanford.edu

  • ↵3 The abbreviations used are: SNP, single nucleotide polymorphism; UTR, untranslated region; DHPLC, denaturing high pressure liquid chromatography; MMR, mismatch repair.

  • ↵4 Available at http://insertion.stanford.edu/melt.html.

  • ↵5 Internet address: http://www.ncbi.nlm.nih.gov/LocusLink/list.cgi.

  • ↵6 L. Svensson and P. J. Oefner, unpublished data.

  • ↵7 Internet address: http://www.ncbi.nlm.nih.gov/BLAST/.

    • Accepted December 3, 2001.
    • Received October 18, 2001.
    • Revision received November 29, 2001.
  • Molecular Cancer Therapeutics
View Full Text
PreviousNext
Back to top
Molecular Cancer Therapeutics: 1 (3)
January 2002
Volume 1, Issue 3
  • Table of Contents
  • 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.
Conservation of the Class I β-Tubulin Gene in Human Populations and Lack of Mutations in Lung Cancers and Paclitaxel-resistant Ovarian Cancers1
(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.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Conservation of the Class I β-Tubulin Gene in Human Populations and Lack of Mutations in Lung Cancers and Paclitaxel-resistant Ovarian Cancers1
Sanja Šale, Raphael Sung, Peidong Shen, Kristine Yu, Yan Wang, George E. Duran, Jong-Hyeok Kim, Tito Fojo, Peter J. Oefner and Branimir I. Sikic
Mol Cancer Ther January 1 2002 (1) (3) 215-225;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Conservation of the Class I β-Tubulin Gene in Human Populations and Lack of Mutations in Lung Cancers and Paclitaxel-resistant Ovarian Cancers1
Sanja Šale, Raphael Sung, Peidong Shen, Kristine Yu, Yan Wang, George E. Duran, Jong-Hyeok Kim, Tito Fojo, Peter J. Oefner and Branimir I. Sikic
Mol Cancer Ther January 1 2002 (1) (3) 215-225;
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
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

  • Prediction of individual response to platinum/paclitaxel combination using novel marker genes in ovarian cancers
  • Low doses of cisplatin or gemcitabine plus Photofrin/photodynamic therapy: Disjointed cell cycle phase-related activity accounts for synergistic outcome in metastatic non–small cell lung cancer cells (H1299)
  • Mesenchymal progenitor cells as cellular vehicles for delivery of oncolytic adenoviruses
Show more Article
  • 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

About MCT

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

Copyright © 2021 by the American Association for Cancer Research.

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

Advertisement