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Updated: Jun 18, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
06:54

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells

Published on: October 27, 2020

Dual effects of TGF-beta on ERalpha-mediated estrogenic transcriptional activity in breast cancer

Yongsheng Ren1, Liyu Wu, Andra R Frost

  • 1Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35249 USA. ysren@uab.edu

Molecular Cancer
|December 1, 2009
PubMed
Abstract

Insights

TGF-beta resistance in breast cancer involves Smad4, which normally suppresses estrogen receptor activity. Aberrant Smad4 expression disrupts this, promoting tumor growth and progression.

Area of Science:

  • Molecular oncology
  • Cancer cell signaling
  • Tumor microenvironment

Background:

  • Breast cancer cells develop TGF-beta resistance, creating an immunosuppressive environment that promotes tumor growth and metastasis.
  • Smad-mediated interactions with the estrogen receptor (ERalpha) are crucial in breast cancer development and progression.

Purpose of the Study:

  • Investigate how TGF-beta regulates ERalpha-induced gene transcription.
  • Elucidate mechanisms behind frequent TGF-beta resistance in breast cancer.

Main Methods:

  • Utilized transient transfection, real-time PCR, sequential DNA precipitation, and siRNA assays in breast cancer cell lines.
  • Assessed Smad expression in cell lines and ERalpha-positive human breast cancer tissue via immunofluorescence and immunohistochemistry.

Main Results:

  • Smad3/4 complex mediates TGF-beta inhibition of ERalpha activity; Smad4 is essential for repression.
  • Smad4 down-regulation and abnormal distribution correlate with ERalpha-positive infiltrating breast carcinoma.
  • Smad4 expression changes dynamically from benign to malignant breast tissue.

Conclusions:

  • Aberrant Smad4 expression or activity disruption leads to loss of TGF-beta's suppression of ERalpha transactivity in breast cancer.
  • These findings highlight Smad4's critical role in TGF-beta resistance and breast cancer progression.

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