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c-Jun N-terminal kinase negatively regulates epidermal growth factor-induced cyclooxygenase-2 expression in oral

Camilla Husvik1, Magne Bryne, Trond S Halstensen

  • 1Department of Oral Biology, University of Oslo, Oslo, Norway.

European Journal of Oral Sciences
|February 4, 2010
PubMed

Insights

c-Jun N-terminal kinase (JNK) negatively regulates epidermal growth factor (EGF)-induced cyclooxygenase-2 (COX-2) expression in oral squamous cell carcinoma. Inhibiting JNK boosts EGF-induced COX-2 transcription via the ERK and p38 pathways.

Area of Science:

  • Molecular Biology
  • Cell Signaling
  • Cancer Research

Background:

  • Cyclooxygenase-2 (COX-2) expression is upregulated by epidermal growth factor (EGF) in squamous cell carcinomas.
  • This upregulation is primarily mediated by the extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 signaling pathways.

Purpose of the Study:

  • To investigate the role of c-Jun N-terminal kinase (JNK) in regulating EGF-induced COX-2 expression in oral squamous cell carcinoma (OSCC).
  • To elucidate the relationship between JNK, ERK1/2, p38 pathways, and COX-2 transcription in OSCC.

Main Methods:

  • Utilized basaloid and conventional OSCC cell lines.
  • Inhibited JNK using the specific inhibitor SP600125.
  • Measured EGF-induced COX-2 transcription.
  • Assessed the involvement of nuclear factor of activated T cells c3 (NFATc3) using cyclosporine A.

Main Results:

  • Inhibition of JNK with SP600125 increased EGF-induced COX-2 transcription by 1.5-1.9 fold in OSCC cell lines.
  • This increase was dependent on the ERK1/2 and p38 signaling pathways.
  • JNK did not appear to be involved in basal COX-2 expression.
  • Cyclosporine A did not affect EGF-induced COX-2 expression, suggesting NFATc3 is not the key mediator in this context.

Conclusions:

  • JNK acts as a negative regulator of EGF-induced COX-2 transcription in OSCC.
  • JNK likely exerts its inhibitory effect through an unidentified phosphatase, influencing the ERK1/2 and/or p38 pathways.
  • These findings highlight a novel regulatory mechanism for COX-2 in oral cancer progression.

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