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Updated: Aug 29, 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

p21(WAF1/CIP1) mediates the growth response to TGF-beta in human epithelial cells

Kurtis E Bachman1, Brian G Blair, Keith Brenner

  • 1The Sidney Kimmel Comprehensive Canter Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Department of Oncology, Baltimore, Maryland 21231, USA.

Cancer Biology & Therapy
|January 17, 2004
PubMed

Insights

Cancers lacking p21 evade TGF-beta

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Transforming growth factor-beta (TGF-beta) is a cytokine that typically inhibits epithelial cell growth.
  • Cancer cells often develop mechanisms to evade TGF-beta's tumor-suppressive functions.

Purpose of the Study:

  • To investigate how cancers evade the growth inhibitory effects of TGF-beta.
  • To elucidate the role of p21 in mediating TGF-beta's effects on cancer cells.

Main Methods:

  • Utilized two human epithelial cell lines with somatically deleted p21 (p21-/-).
  • Analyzed TGF-beta's effect on cell growth and phenotype in p21-/- cells.
  • Examined vimentin and E-cadherin expression.
  • Conducted immunohistochemical analysis of primary human breast cancers.

Main Results:

  • TGF-beta stimulated growth in p21-/- cells, acting as a growth promoter instead of a suppressor.
  • p21-/- cells treated with TGF-beta displayed a mesenchymal phenotype, with increased vimentin and decreased E-cadherin.
  • A correlation was observed between p21 loss and positive vimentin expression in human breast cancers.

Conclusions:

  • Loss of p21 enables cancer cells to escape TGF-beta's anti-proliferative effects.
  • TGF-beta can promote cancer growth and a mesenchymal phenotype in the absence of p21.
  • This mechanism contributes to non-gastrointestinal cancer progression and growth advantage.

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