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Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog
08:37

Fluorescence-based Monitoring of PAD4 Activity via a Pro-fluorescence Substrate Analog

Published on: November 5, 2014

A novel transformation suppressor, Pdcd4, inhibits AP-1 transactivation but not NF-kappaB or ODC transactivation

H S Yang1, A P Jansen, R Nair

  • 1Gene Regulation Section, Basic Research Laboratory, National Cancer Institute, Frederick, MD 21702, USA.

Oncogene
|April 21, 2001
PubMed

Insights

Programmed cell death 4 (Pdcd4) suppresses neoplastic transformation by inhibiting AP-1 activation. Overexpressing Pdcd4 in susceptible cells confers resistance to tumor promoters, suggesting its potential as a cancer prevention target.

Area of Science:

  • Molecular biology
  • Cancer research
  • Cell signaling

Background:

  • Programmed cell death 4 (Pdcd4) is a transformation suppressor highly expressed in promotion-resistant mouse epidermal JB6 cells.
  • Susceptible (P+) cells lack high Pdcd4 expression, indicating its role in transformation resistance.

Purpose of the Study:

  • To investigate if Pdcd4 suppresses neoplastic transformation by inhibiting key events like AP-1 and NF-kappaB activation or ornithine decarboxylase (ODC) activity.
  • To determine if elevated Pdcd4 expression is sufficient to prevent tumor promoter-induced transformation.

Main Methods:

  • Stable transfection of Pdcd4 cDNA into susceptible P+ cells.
  • Assays to measure AP-1 and NF-kappaB dependent transcriptional activity.
  • Measurement of ornithine decarboxylase (ODC) enzymatic activity.

Main Results:

  • Overexpression of Pdcd4 in P+ cells conferred resistance to tumor promoter-induced transformation.
  • Pdcd4 inhibited AP-1 dependent transcriptional activity in a concentration-dependent manner.
  • Pdcd4 slightly increased NF-kappaB dependent transcription and did not affect ODC activity.

Conclusions:

  • Pdcd4 acts as a transformation suppressor, likely by inhibiting AP-1 activation.
  • Enhanced Pdcd4 expression may suppress neoplastic transformation through combined effects on AP-1 and NF-kappaB signaling.
  • Pdcd4 represents a potential molecular target for cancer prevention strategies.

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