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c-Myc induces cellular susceptibility to the cytotoxic action of TNF-alpha

J Klefstrom1, I Västrik, E Saksela

  • 1Department of Pathology, University of Helsinki, Finland.

The EMBO Journal
|November 15, 1994
PubMed

Insights

Increased c-Myc oncoprotein expression enhances tumor cells

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Tumor necrosis factor-alpha (TNF) is a cytokine with cytotoxic effects on tumor cells.
  • The mechanisms underlying TNF sensitivity in transformed cells remain unclear.
  • c-Myc oncoprotein is frequently deregulated in human cancers.

Purpose of the Study:

  • To investigate the role of c-Myc oncoprotein in modulating cellular sensitivity to TNF.
  • To elucidate the molecular mechanisms linking c-Myc and TNF-induced cytotoxicity.

Main Methods:

  • Utilized Rat1A and NIH3T3 fibroblasts with varying c-Myc expression levels.
  • Employed a hormone-inducible c-Myc-estrogen receptor chimera (MycER) for controlled c-Myc activation.
  • Investigated the effects of Bcl2 oncoprotein and Mn superoxide dismutase.
  • Used antisense c-myc oligodeoxynucleotides in fibrosarcoma cells.

Main Results:

  • Overexpression of c-Myc significantly increased sensitivity to TNF-induced apoptosis in resistant fibroblasts.
  • c-Myc and TNF-induced apoptosis was attenuated by Bcl2 and Mn superoxide dismutase.
  • Antisense inhibition of c-Myc reduced TNF cytotoxicity in sensitive fibrosarcoma cells.

Conclusions:

  • Deregulation of c-Myc oncogene is a key factor contributing to TNF sensitivity in tumor cells.
  • c-Myc enhances TNF-induced apoptosis, potentially through pathways involving oxidative stress and Bcl2.
  • Targeting c-Myc could be a strategy to modulate TNF efficacy in cancer therapy.

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