Prostaglandin synthase 2 expression in epidermal growth factor-dependent proliferation of mouse keratinocytes

Charles D. Loftin, Thomas E. Eling

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

BALB/c mouse keratinocytes (BALB/MK) are nontumorigenic epithelial cells which are dependent on mouse epidermal growth factor (EGF) for maintaining proliferation in culture. In BALB/MK the oxygenation of both arachidonic acid and linoleic acid was dependent on EGF. EGF stimulated the formation of prostaglandin E2 and prostaglandin F(2α) from arachidonic acid and 9- and 13-hydroxyoctadecadienoic acid (HODE) from linoleic acid. Analysis of the linoleic acid metabolites determined the ratio of 9-HODE to 13-HODE was approximately 6 to 4, and the 9-HODE was the (R) enantiomer, consistent with metabolism by prostaglandin G/H synthase (PGHS). The formation of these linoleic acid metabolites was sensitive to indomethacin, a PGHS inhibitor. EGF induced the expression of PGHS-2 mRNA after 30 min, which peaked after 1 h, and remained expressed for at least 24 h after the addition of EGF. A less significant increase in the expression of PGHS-1 mRNA occurred 4 h after EGF stimulation. Immunoblot analysis did not detect expression of PGHS-1 protein. However, PGHS-2 protein expression was increased 2 h after EGF exposure and was dependent on EGF. PGHS-2 protein was not transiently expressed as reported with other cell types, but was continually expressed in proliferating cells maintained with EGF at a subconfluent density. Indomethacin significantly attenuated EGF-dependent mitogenesis and cell proliferation. These results suggest that PGHS-2 activity contributes to the proliferative response of BALB/MK to EGF.

Original languageEnglish
Pages (from-to)419-429
Number of pages11
JournalArchives of Biochemistry and Biophysics
Volume330
Issue number2
DOIs
StatePublished - Jun 15 1996

Bibliographical note

Copyright:
Copyright 2017 Elsevier B.V., All rights reserved.

Keywords

  • HODE
  • arachidonic acid
  • epidermal growth factor
  • keratinocytes
  • linoleic acid
  • mitogenesis
  • prostaglandin synthase 2
  • prostaglandins

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

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