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Troglitazone induction of COX-2 expression is dependent on ERK activation in keratinocytes

Guobin He1, You Me Sung, Susan M Fischer

  • 1Department of Carcinogenesis, Science Park-Research Division, University of Texas M.D. Anderson Cancer Center, 1808 Park Road 1C, P.O. Box 389, Smithville, TX 78957, USA.

Prostaglandins, Leukotrienes, and Essential Fatty Acids
|February 1, 2006
PubMed

Insights

Troglitazone, an antidiabetic drug, increases cyclooxygenase-2 (COX-2) and prostaglandin E2 (PGE2) in skin cells. This induction is mediated by the ERK pathway, independent of PPARgamma.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Dermatology

Background:

  • Cyclooxygenase-2 (COX-2) is implicated in skin tumorigenesis.
  • Understanding the regulation of COX-2 in skin cells is crucial for cancer research.

Purpose of the Study:

  • To investigate the effect of troglitazone on COX-2 expression in keratinocytes.
  • To elucidate the signaling pathways involved in troglitazone-induced COX-2 expression.

Main Methods:

  • Cultured mouse skin keratinocytes were treated with troglitazone.
  • COX-2 and prostaglandin E2 (PGE2) levels were measured.
  • Peroxisome proliferator-activated receptor gamma (PPARgamma) independence was assessed.
  • Extracellular signal-regulated kinase (ERK) phosphorylation was analyzed.
  • Specific inhibitors of ERK activation were used to block COX-2 induction.

Main Results:

  • Troglitazone significantly increased COX-2 protein and mRNA levels in keratinocytes.
  • Troglitazone elevated the production of PGE2.
  • The induction of COX-2 by troglitazone was independent of PPARgamma.
  • Troglitazone treatment led to sustained ERK phosphorylation.
  • Inhibiting ERK activation largely prevented troglitazone-induced COX-2 expression.

Conclusions:

  • Troglitazone induces COX-2 expression and PGE2 production in mouse skin keratinocytes.
  • The mechanism is dependent on the ERK signaling pathway.
  • This effect appears to be independent of PPARgamma activation.

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