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Updated: Jul 10, 2026

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling
07:49

Molecular Analysis of Endothelial-mesenchymal Transition Induced by Transforming Growth Factor-β Signaling

Published on: August 3, 2018

Cyclooxygenase-2 overexpression abrogates the antiproliferative effects of TGF-beta

G A Enders1

  • 1Institute for Surgical Research, LMU-München, Marchioninistr. 27, München D-81366, Germany. enders@med.uni-muenchen.de

British Journal of Cancer
|October 24, 2007
PubMed

Insights

Cyclooxygenase-2 (COX-2) overexpression abrogates transforming growth factor-beta (TGF-beta) growth inhibition by upregulating TGF-alpha and ERK signaling. Targeting COX-2, PPAR, and TGF/EGF pathways may prevent intestinal tumor development.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Cyclooxygenase-2 (COX-2) overexpression is linked to tumor development, but mechanisms remain unclear.
  • TGF-beta normally inhibits cell proliferation, particularly in the intestine.
  • COX-2's role in cell growth regulation and its interaction with TGF-beta signaling require further elucidation.

Purpose of the Study:

  • To investigate the mechanism by which COX-2 overexpression influences TGF-beta's growth inhibitory effects.
  • To determine if COX-2 affects the TGF-beta/Smad signaling pathway.
  • To identify alternative pathways activated by COX-2 that may promote cell proliferation.

Main Methods:

  • Transfection of a TGF-beta-sensitive cell line with COX-2.
  • Analysis of the TGF-beta/Smad signaling pathway (receptor expression, Smad phosphorylation).
  • TGF-beta reporter assays, TGF-alpha expression analysis, ERK 1/2 pathway assessment, and PPAR signaling reporter assays.

Main Results:

  • COX-2 transfection abrogated TGF-beta's growth inhibitory effects without interfering with the TGF-beta/Smad pathway.
  • COX-2 overexpression induced TGF-alpha expression and prolonged ERK 1/2 pathway stimulation.
  • Increased PPAR signaling was observed in COX-2 transfectants, suggesting a role for lipid mediators.

Conclusions:

  • COX-2 promotes proliferation by counteracting TGF-beta's inhibition through alternative pathways, including TGF-alpha/ERK and potentially PPAR signaling.
  • Combined inhibition of COX-2, PPAR, and TGF/EGF pathways may offer a strategy for preventing intestinal adenoma and carcinoma.
  • Understanding these complex interactions is crucial for developing targeted cancer therapies.

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