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The oncogene PDGF-B provides a key switch from cell death to survival induced by TNF

P Y Billie Au1, Nicole Martin, Hien Chau

  • 1AMDI/cFIFBCR, University Health Network, Department of Medical Biophysics, University of Toronto, 620 University Ave. Suite 7-706, Toronto, Ontario, Canada M5G 2C1.

Oncogene
|March 1, 2005
PubMed

Insights

Tumor necrosis factor (TNF) activates NF-kappaB, which upregulates platelet-derived growth factor B (PDGF-B) as a survival gene. Cancer cells may exploit this PDGF-B pathway to evade TNF-induced death.

Area of Science:

  • Cellular biology
  • Molecular oncology
  • Signal transduction

Background:

  • Tumor necrosis factor (TNF) triggers both cell death and survival pathways.
  • Nuclear factor-kappaB (NF-kappaB) is a key transcription factor mediating TNF-induced survival signals.
  • Identification of NF-kappaB target genes with oncogenic roles is crucial.

Purpose of the Study:

  • To investigate the role of NF-kappaB target genes in mediating TNF-induced survival signals.
  • To determine if platelet-derived growth factor B (PDGF-B) is an NF-kappaB-regulated survival gene.
  • To explore the implications of PDGF-B signaling in cancer cell survival.

Main Methods:

  • Utilized fibroblasts and NIH-3T3 cells.
  • Measured TNF-induced gene expression.
  • Assessed cell viability under various treatment conditions (TNF, PDGF-B inhibition).
  • Investigated NF-kappaB dependency.

Main Results:

  • TNF strongly induces PDGF-B in fibroblasts via an NF-kappaB-dependent mechanism.
  • PDGF-B rescues NF-kappaB-deficient cells from TNF-induced death.
  • Inhibiting PDGF-B signaling sensitizes normal and PDGF-B-transformed cells to TNF-induced death.
  • Tumor cells may rely on upregulated PDGF-B for survival against TNF.

Conclusions:

  • PDGF-B is a critical NF-kappaB-regulated survival gene induced by TNF.
  • Cancer cells might depend on abnormally upregulated PDGF-B to evade TNF-mediated apoptosis.
  • Targeting PDGF-B signaling could be a therapeutic strategy against cancers evading TNF-induced death.

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