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The mitogenic response of AML blasts to tumor necrosis factor-alpha requires functional c-jun/AP-1

M A Brach1, F Herrmann

  • 1Max-Delbrück-Centrum für Molekulare Medizin, Berlin, Germany.

Leukemia
|August 1, 1993
PubMed

Insights

Tumor Necrosis Factor-alpha (TNF-alpha) stimulates acute myelogenous leukemia (AML) cell proliferation by activating c-jun. Antisense oligomers targeting c-jun blocked this TNF-alpha-induced growth, confirming c-jun

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Signaling

Background:

  • The c-jun proto-oncogene is an immediate early response gene.
  • c-jun is induced by growth factors and Tumor Necrosis Factor (TNF).
  • The role of c-jun in acute myelogenous leukemia (AML) cell proliferation requires elucidation.

Purpose of the Study:

  • To investigate the role of c-jun in the mitogenic response of AML blasts to TNF-alpha.
  • To determine if c-jun activation is essential for TNF-alpha-mediated growth stimulation in AML.

Main Methods:

  • Treatment of primary AML blasts with TNF-alpha.
  • Assessment of c-jun transcriptional activation and mRNA accumulation.
  • Utilized antisense (AS) oligomers targeting the c-jun translation initiation site to block c-jun/AP-1 activity.
  • Compared AS oligomers with sense (S) and non-sense (NS) controls for specificity.
  • Evaluated the proliferative response of AML blasts to TNF-alpha under different oligomer treatments.

Main Results:

  • TNF-alpha treatment induced c-jun transcriptional activation and mRNA accumulation in AML blasts.
  • AS oligomers specifically blocked c-jun/AP-1 translation, while S and NS oligomers did not.
  • AML blasts treated with AS c-jun oligomers failed to proliferate in response to TNF-alpha stimulation.
  • S and NS oligomers did not inhibit the proliferative response to TNF-alpha.

Conclusions:

  • Activation of c-jun/AP-1 is crucial for the proliferative response of AML cells to TNF-alpha.
  • c-jun plays a pivotal role in the signaling cascade initiated by TNF-alpha, leading to cell proliferation.
  • Targeting c-jun with antisense technology offers a potential strategy for modulating AML cell growth.

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