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
Regular Articles

Alterations in Transforming Growth Factor-α and -β Production and Cell Responsiveness during the Progression of MCF-7 Human Breast Cancer Cells to Estrogen-Autonomous Growth

Mary E. Herman and Benita S. Katzenellenbogen
Mary E. Herman
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Benita S. Katzenellenbogen
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
DOI:  Published November 1994
  • Article
  • Info & Metrics
  • PDF
Loading

Abstract

Hormonal management of breast cancer is confounded by an almost inevitable progression of cell growth from a steroid-regulated to a steroid-autonomous state. We have experimentally induced this progression in the estrogen growth-responsive MCF-7 human breast cancer cell line by long-term culture in the absence of steroids. After an initial period (10–12 weeks) of slowed growth in response to steroid deprivation, rapid, steroid-independent growth rates were consistently established. In these cells, which contained 3-fold elevated, functional estrogen receptor levels (as determined by induction of PgR and transactivation of a transiently transfected estrogen-responsive gene construct), antiestrogens still effectively suppressed cell proliferation, although estrogens only minimally increased the proliferation rate. Depletion of steroids from the growth media also resulted in a marked (70–80%) transient decrease in transforming growth factor (TGF) α mRNA and TGF-α protein production at 2 weeks that was followed by a progressive, partial return to the initial parental TGF-α mRNA and protein levels. In contrast, the mRNAs for TGF-β1,-β2, and -β3 and bioactive TGF-β proteins transiently increased (3–10-fold) at 2 to 10 weeks of steroid deprivation and then returned by 24 weeks to the lower levels of the parental MCF-7 cells. These results suggest that the cells acquired steroid-independent means to regulate the production of these peptides. The long-term steroid-deprived sublines showed a loss of regulation of proliferation by TGF-α or anti-TGF-α antibodies and a 10-fold decrease in sensitivity to the growth-suppressive effects of TGF-β1, despite little change in receptor levels for these factors. The diminished contributions of TGF-α and TGF-βs to the regulation of cell proliferation in long-term steroid-deprived MCF-7 breast cancer cells suggest that the TGFs do not act as major growth regulators in these estrogen-autonomous sublines. However, the marked, transient alterations in the levels of these growth factors indicate that they may play a role in the events which accompany the progression from estrogen-responsive to estrogen-autonomous growth. In addition, continued exposure to estrogen may be needed for the long-term maintenance of cell responsiveness to these TGFs.

Footnotes

  • ↵1 Supported in part by NIH Grants CA18119 and CA51482 (to B. S. K.), predoctoral fellowship GM07283, and Carle Foundation Cancer Research Funds (to M. E. H.), and a Susan G. Komen Foundation grant.

  • ↵2 To whom requests for reprints should be addressed, at Department of Physiology and Biophysics, University of Illinois, 524 Burrill Hall, 407 S. Goodwin Ave., Urbana, IL 61801.

  • Received June 30, 1994.
  • Accepted September 29, 1994.
  • ©1994 American Association for Cancer Research.
PreviousNext
Back to top
November 1994
Volume 54, Issue 22
  • Table of Contents
  • Table of Contents (PDF)
  • Index by Author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)

Sign up for alerts

Open full page PDF
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.
Alterations in Transforming Growth Factor-α and -β Production and Cell Responsiveness during the Progression of MCF-7 Human Breast Cancer Cells to Estrogen-Autonomous Growth
(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
Alterations in Transforming Growth Factor-α and -β Production and Cell Responsiveness during the Progression of MCF-7 Human Breast Cancer Cells to Estrogen-Autonomous Growth
Mary E. Herman and Benita S. Katzenellenbogen
Cancer Res November 15 1994 (54) (22) 5867-5874;

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Alterations in Transforming Growth Factor-α and -β Production and Cell Responsiveness during the Progression of MCF-7 Human Breast Cancer Cells to Estrogen-Autonomous Growth
Mary E. Herman and Benita S. Katzenellenbogen
Cancer Res November 15 1994 (54) (22) 5867-5874;
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
  • PDF
Advertisement

Related Articles

Cited By...

More in this TOC Section

Regular Articles

  • Phase I Trial of Intraperitoneal Iododeoxyuridine with and without Intravenous High-Dose Folinic Acid in the Treatment of Advanced Malignancies Primarily Confined to the Peritoneal Cavity: Flow Cytometric and Pharmacokinetic Analysis
  • Mitochondrial Membrane Potential (ΔΨmt) in the Coordination of p53-independent Proliferation and Apoptosis Pathways in Human Colonic Carcinoma Cells
  • Death of Tumor Cells after Intracellular Acidification Is Dependent on Stress-activated Protein Kinases (SAPK/JNK) Pathway Activation and Cannot Be Inhibited by Bcl-2 Expression or Interleukin 1β-converting Enzyme Inhibition
Show more 3

Endocrinology

  • Abstract LB-257: Estrogen signaling in mature luminal and luminal progenitor cells of BRCA2 carriers and non-carriers
  • Abstract LB-259: Pb203-AR-RMX conjugates for image-guided TAT of neuroendocrine tumors (NETs)
  • Abstract LB-258: Orphan nuclear hormone receptor, DAX-1, expression during progressive stages of invasive ductal carcimona
Show more 3

Articles

  • Abstract LB-257: Estrogen signaling in mature luminal and luminal progenitor cells of BRCA2 carriers and non-carriers
  • Abstract LB-259: Pb203-AR-RMX conjugates for image-guided TAT of neuroendocrine tumors (NETs)
  • Abstract LB-258: Orphan nuclear hormone receptor, DAX-1, expression during progressive stages of invasive ductal carcimona
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