Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
The type III TGF-β receptor suppresses breast cancer progression
Mei Dong, … , Jeffrey R. Marks, Gerard C. Blobe
Mei Dong, … , Jeffrey R. Marks, Gerard C. Blobe
Published January 2, 2007
Citation Information: J Clin Invest. 2007;117(1):206-217. https://doi.org/10.1172/JCI29293.
View: Text | PDF
Research Article Oncology

The type III TGF-β receptor suppresses breast cancer progression

  • Text
  • PDF
Abstract

The TGF-β signaling pathway has a complex role in regulating mammary carcinogenesis. Here we demonstrate that the type III TGF-β receptor (TβRIII, or betaglycan), a ubiquitously expressed TGF-β coreceptor, regulated breast cancer progression and metastasis. Most human breast cancers lost TβRIII expression, with loss of heterozygosity of the TGFBR3 gene locus correlating with decreased TβRIII expression. TβRIII expression decreased during breast cancer progression, and low TβRIII levels predicted decreased recurrence-free survival in breast cancer patients. Restoring TβRIII expression in breast cancer cells dramatically inhibited tumor invasiveness in vitro and tumor invasion, angiogenesis, and metastasis in vivo. TβRIII appeared to inhibit tumor invasion by undergoing ectodomain shedding and producing soluble TβRIII, which binds and sequesters TGF-β to decrease TGF-β signaling and reduce breast cancer cell invasion and tumor-induced angiogenesis. Our results indicate that loss of TβRIII through allelic imbalance is a frequent genetic event during human breast cancer development that increases metastatic potential.

Authors

Mei Dong, Tam How, Kellye C. Kirkbride, Kelly J. Gordon, Jason D. Lee, Nadine Hempel, Patrick Kelly, Benjamin J. Moeller, Jeffrey R. Marks, Gerard C. Blobe

×

Figure 8

TβRIII attenuates Smad2 phosphorylation in vitro and in vivo.

Options: View larger image (or click on image) Download as PowerPoint
TβRIII attenuates Smad2 phosphorylation in vitro and in vivo.
(A) TβRIII...
(A) TβRIII-overexpressing and control MDA-MB231 cells were treated with TGF-β1 under the indicated conditions, and cell lysates were analyzed with a phospho-Smad2 (p-Smad2) antibody. (B) Cells were transfected with pE2.1 and pSVβ vector. Luciferase activity was determined after 24 hours of TGF-β1 treatment (100 pM) and is expressed as the fold induction over no TGF-β treatment after adjusting for β-galactosidase expression. This assay was performed in triplicate at least 3 times. *P < 0.05. (C) Phosphorylated Smad2 immunostaining of tissue sections from 4T1-Neo and 4T1-TβRIII primary tumors. Representative results are shown. Note the significant decrease in staining intensity in the 4T1-TβRIII tumor. Original magnification, ×40.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts