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
Endocrinology 5: Endocrinology V

Long-term fulvestrant treatment results in irreversible loss of estrogen receptor alpha expression in MCF-7 human breast cancer cells

Hong Liu, Laura Wing, Alexander De Los Reyes and V. Craig Jordan
Hong Liu
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Laura Wing
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alexander De Los Reyes
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
V. Craig Jordan
Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published April 2004
  • Article
  • Info & Metrics
Loading
Proc Amer Assoc Cancer Res, Volume 45, 2004

Abstract

5600

Fulvestrant (Faslodex®, ICI 182,780) is a steroidal pure antiestrogen. It has a high binding affinity to the estrogen receptor alpha (ERα), competitively inhibits the binding of estrogen to the ER, and blocks ER dimerization. Moreover, it causes ER degradation. Fulvestrant has no known agonist activity, and has been approved for the treatment of breast cancer which has progressed on prior antiestrogen therapy in postmenopausal women. Although this treatment will provide clinical benefit for women with advanced breast cancer, fulvestrant resistant disease will eventually occur. To understand the mechanism of fulvestrant resistance in order to evaluate further treatments, we developed a unique fulvestrant resistant model (MCF-7/ICI) using MCF-7 ERα positive human breast cancer cells by culturing the cells for twelve months in estrogen-free medium containing 1 μM fulvestrant to mimic postmenopausal conditions. MCF-7/ICI cells had become ERα negative as determined by real-time RT-PCR, Western blot analysis, and ERE-luciferase transfection assays. ERβ mRNA expression level did not change compared to the parental MCF-7 cells measured by real-time RT-PCR. Both parental MCF-7 and MCF-7/ICI cells were essentially ERβ negative as the mRNA ratio of ERβ:ERα was 1:7500. Interestingly, MCF-7/ICI cells remained ER negative after withdrawal of fulvestrant and switching the culture medium back to whole serum (estrogen con taining) medium for twelve months. Analysis of factors that may have been altered in the MCF-7/ICI cells showed that phosphorylation of p44/42MAPK was significantly increased compared to parental cells. We also found that the MCF-7/ICI cells expressed significantly higher levels of epithelial growth factor (EGF) receptor mRNA and protein, as determined by real-time RT-PCR and Western blot analysis, respectively. However, EGFR overexpression was not due to gene amplification as indicated by FISH (Fluorescence in situ Hybridization) analysis. Consistent with EGFR overexpression, a specific EGFR tyrosine kinase inhibitor, Iressa (ZD1839), preferentially inhibits the growth of MCF-7/ICI cells relative to the parental MCF-7 cells in a dose dependent manner, which is consistent with a previous report (R.A. McClelland, et al. Endocrinology, 142:2776-88, 2001). In conclusion, MCF-7/ICI cells are the first MCF-7 subline to show irreversibly loss of ER expression after extended treatment of fulvestrant. The factors involving EGF receptor signaling transduction pathway are the potential targets for controlling the growth of MCF-7/ICI cells and may have clinical implications for further management of fulvestrant resistant ERα negative breast cancer. This work was supported by the Avon Foundation, the Lynn Sage Cancer Research Foundation, and the NIH SPORE in Breast Cancer CA 89018-03.

  • American Association for Cancer Research
Previous
Back to top
April 2004
Volume 64, Issue 7 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.
Long-term fulvestrant treatment results in irreversible loss of estrogen receptor alpha expression in MCF-7 human 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
Long-term fulvestrant treatment results in irreversible loss of estrogen receptor alpha expression in MCF-7 human breast cancer cells
Hong Liu, Laura Wing, Alexander De Los Reyes and V. Craig Jordan
Cancer Res April 1 2004 (64) (7 Supplement) 1293-1294;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Long-term fulvestrant treatment results in irreversible loss of estrogen receptor alpha expression in MCF-7 human breast cancer cells
Hong Liu, Laura Wing, Alexander De Los Reyes and V. Craig Jordan
Cancer Res April 1 2004 (64) (7 Supplement) 1293-1294;
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

  • Psoriasin: A possible downstream marker of estrogen receptor β1 activity in human breast cancer cells
  • Ligand-independent, MAPK-dependent activation and serine phosphorylation of wild-type (67 kDa) and delta7 (∼52 kDa) isoform of estrogen receptor alpha by the redox active quinone, vitamin K3/menadione
Show more Endocrinology 5: Endocrinology V
  • 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