Skip to main content
  • AACR Publications
    • 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
Advertisement

Main menu

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
  • AACR Publications
    • 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

Search

  • Advanced search
Cancer Research
Cancer Research

Advanced Search

  • Home
  • About
    • The Journal
    • AACR Journals
    • Subscriptions
    • Permissions and Reprints
    • Reviewing
  • Articles
    • OnlineFirst
    • Current Issue
    • Past Issues
    • Focus on Computer Resources
    • 75th Anniversary
    • Meeting Abstracts
  • For Authors
    • Information for Authors
    • Author Services
    • Best of: Author Profiles
    • Submit
  • Alerts
    • Table of Contents
    • OnlineFirst
    • Editors' Picks
    • Citations
    • Author/Keyword
  • News
    • Cancer Discovery News
Poster Session Abstracts

Src-Dependent Changes in Beta-Catenin Activity Promote a Migratory Phenotype in Endocrine-Resistant Breast Cancer Cells.

A. Wadhawan, P. Barrett-Lee, C. Smith, R. Nicholson and S. Hiscox
A. Wadhawan
Velindre Cancer Centre, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
P. Barrett-Lee
Velindre Cancer Centre, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Smith
Welsh School of Pharmacy, Cardiff University, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
R. Nicholson
Welsh School of Pharmacy, Cardiff University, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
S. Hiscox
Welsh School of Pharmacy, Cardiff University, United Kingdom
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI: 10.1158/0008-5472.SABCS-09-5143 Published December 2009
  • Article
  • Info & Metrics
Loading
Abstracts: Thirty-Second Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 10‐13, 2009; San Antonio, TX

Abstract

Background: Acquired resistance to endocrine therapies is associated with disease relapse and progression. In vitro, endocrine resistance is accompanied by increased Src activity and the development of a highly invasive and migratory phenotype. Here we have investigated the role of Src as a modulator of intercellular adhesion in endocrine-resistant breast cancer cells.Methods: Src and beta-catenin expression and activity were determined in endocrine-sensitive MCF7 and T47D cells and tamoxifen-resistant ('TamR') MCF7 cell variants at their basal level and following treatment with the Src inhibitor AZD0530 (0-2µM) using Western Blotting. Cell migration was assessed by seeding cells onto matrix-coated porous membranes in the presence or absence of AZD0530. After 24hrs, migratory cells were fixed, stained and counted. The effects of Src inhibition on beta-catenin association with E-cadherin was measured by immunoprecipitation whilst changes in cell morphology were determined using differential interference contrast microscopy.Results: In contrast to endocrine-sensitive MCF7 cells, tamoxifen-resistant ('TamR') variants displayed high levels of both activated Src kinase (Src phosphorylated at Y419) and tyrosine-phosphorylated beta-catenin (Y142 and Y654). Accompanying this was a decrease in the association of beta-catenin with E-cadherin; TamR cells also grew as dispersed cell colonies and displayed a greatly enhanced migratory phenotype compared to MCF7 cells. Inhibition of Src in TamR cells significantly reduced both Src activity and levels of beta-catenin (Y142 and Y654) whilst restoring beta-catenin association with E-cadherin and suppressing cell migration. Immunohistochemistry studies involving ER+ve breast cancer tissue (n=390 from the ABC trial) have revealed that higher nuclear levels of y142 phosphorylated beta-catenin correlate with increased levels of total beta-catenin in the nuclei, suggesting src activated beta-catenin may confer an aggressive breast cancer phenotype.Treatment of ER+ve, endocrine-sensitive MCF7 and T47D cells with tamoxifen in the short term promoted an increase in Src activity and an accompanying Src-dependent increase in tyrosine-phosphorylated Y142 and Y654 beta-catenin, No effect was seen following treatment with fulvestrant or upon oestrogen deprivation.Conclusion: Src-dependent changes in beta catenin phosphorylation status appear to play a central role in the development of the migratory nature accompanying tamoxifen resistance in breast cancer cells which may correlate with findings in clinical tissue. Importantly, Src-dependent changes in beta-catenin activity appear to be promoted by tamoxifen itself during the drug-responsive phase and can be suppressed by the concomitant use of Src inhibitors.

Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5143.

Back to top
Cancer Research: 69 (24 Supplement)
December 2009
Volume 69, Issue 24 Supplement
  • Table of Contents
  • Index by Author

Sign up for alerts

Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Cancer Research 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.
Src-Dependent Changes in Beta-Catenin Activity Promote a Migratory Phenotype in Endocrine-Resistant Breast Cancer Cells.
(Your Name) has forwarded a page to you from Cancer Research
(Your Name) thought you would be interested in this article in Cancer Research.
Citation Tools
Src-Dependent Changes in Beta-Catenin Activity Promote a Migratory Phenotype in Endocrine-Resistant Breast Cancer Cells.
A. Wadhawan, P. Barrett-Lee, C. Smith, R. Nicholson and S. Hiscox
Cancer Res December 15 2009 (69) (24 Supplement) 5143; DOI: 10.1158/0008-5472.SABCS-09-5143

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Src-Dependent Changes in Beta-Catenin Activity Promote a Migratory Phenotype in Endocrine-Resistant Breast Cancer Cells.
A. Wadhawan, P. Barrett-Lee, C. Smith, R. Nicholson and S. Hiscox
Cancer Res December 15 2009 (69) (24 Supplement) 5143; DOI: 10.1158/0008-5472.SABCS-09-5143
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
  • Info & Metrics
Advertisement

Related Articles

Cited By...

More in this TOC Section

Poster Session Abstracts

  • Abstract P6-08-04: National trends in mastectomy for operable breast cancers treated with neoadjuvant chemotherapy
  • Abstract P6-15-12: A functional approach to the molecular basis of neoadjuvant treatment response in breast cancer
  • Abstract P6-14-06: Oral etoposide (VP-16) in heavily pre-treated metastatic breast cancer: A multicenter national observational study
Show more 3

Poster Session 5 - Tumor Biology

  • Molecular Heterogeneity of Grade 3 Breast Cancer.
  • Mutant PIK3CA Is Detected in Both Pre-Invasive and Recurrent Breast Cancer.
  • Genetic Contribution of GADD45A to Susceptibility to Sporadic and Non-BRCA1/2 Familial Breast Cancers: A Systemic Evaluation in Chinese Populations.
Show more 3

Tumor Biology - Endocrine Therapy and Resistance

  • CYR61, Estrogen Receptor and FOXO3a: The Interplay in Aggressive Breast Carcinomas.
  • CD44-Activated HER-2 Signalling in Tamoxifen Resistant Breast Cancer Cells Promotes a Migratory Phenotype.
  • Different Treatment Benefit for Luminal A and Luminal B Advanced Breast Cancinomas Receiving Aromatase Inhibitors.
Show more 3
  • Home
  • Alerts
  • Feedback
Facebook  Twitter  LinkedIn  YouTube  RSS

Articles

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

Info for

  • Authors
  • Subscribers
  • Advertisers
  • Librarians
  • Reviewers

About Cancer Research

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

Copyright © 2018 by the American Association for Cancer Research.

Cancer Research Online ISSN: 1538-7445
Cancer Research Print ISSN: 0008-5472
Journal of Cancer Research ISSN: 0099-7013
American Journal of Cancer ISSN: 0099-7374

Advertisement