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IGF-II-mediated COX-2 gene expression in human keratinocytes through extracellular signal-regulated kinase pathway

Hye Jung Kim1, Tae-Yoon Kim

  • 1Department of Dermatology, The Catholic University of Korea, Kangnam St Mary's Hospital, 505 Banpo-dong, Seocho-gu, Seoul, South Korea.

The Journal of Investigative Dermatology
|August 12, 2004
PubMed

Insights

Insulin-like growth factor-II (IGF-II) upregulates cyclooxygenase-2 (COX-2) in keratinocytes via tyrosine kinase, Src, PI3-kinase, ERK, and JNK1 pathways, but not p38. Basal JNK activity is crucial for this IGF-II induced COX-2 expression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Cyclooxygenase-2 (COX-2) plays a role in cellular processes.
  • Insulin-like growth factor-II (IGF-II) is implicated in cell growth and signaling.
  • Understanding IGF-II's regulation of COX-2 is important for cellular function.

Purpose of the Study:

  • To investigate the signaling pathways mediating IGF-II-induced COX-2 expression in human keratinocytes.
  • To elucidate the roles of specific kinases, including tyrosine kinase, Src, PI3-kinase, ERK, JNK1, and p38, in this process.

Main Methods:

  • Treatment of human keratinocytes with IGF-II.
  • Analysis of COX-2 mRNA and protein levels.
  • Use of specific kinase inhibitors (tyrosine kinase, Src, PI3-kinase, ERK, JNK1, p38).
  • COX-2 promoter activity assays using dominant-negative plasmids (MEK1, p38, JNK1).

Main Results:

  • IGF-II significantly increased COX-2 mRNA and protein levels.
  • Inhibitors of tyrosine kinase, Src, PI3-kinase, ERK, and JNK1 reduced IGF-II-induced COX-2 expression.
  • p38 inhibition did not affect IGF-II-induced COX-2 expression.
  • COX-2 promoter activity was increased by IGF-II, an effect blocked by dominant-negative MEK1 and JNK1, but not p38.
  • Inhibition of ERK or JNK1 reduced IGF-II-induced prostaglandin E(2) synthesis and cell proliferation.

Conclusions:

  • IGF-II induces COX-2 expression in keratinocytes through tyrosine kinase-Src-ERK and tyrosine kinase-PI3-kinase signaling pathways.
  • The p38 MAPK pathway is not involved in IGF-II-induced COX-2 expression.
  • Basal JNK activity is essential for the upregulation of COX-2 by IGF-II.

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