Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells

Juan R. Mestre, Kotha Subbaramaiah, Peter G. Sacks, Stimson P. Schantz, Tadashi Tanabe, Hiroyasu Inoue, Andrew J. Dannenberg

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Cyclooxygenase-2 (Cox-2), the inducible form of cyclooxygenase, is up- regulated in tumors and transformed cells. Because this enzyme catalyzes the formation of prostaglandins from arachidonic acid, chemopreventive strategies that suppress its expression could be useful for preventing cancer. We investigated whether retinoids suppressed basal expression of Cox-2 or EGF- mediated induction of Cox-2 in human oral squamous carcinoma cells. Treatment with retinoids [all-trans-retinoic acid (all-trans-RA), 9-cis-RA, 13-cis-RA, and retinyl acetate] suppressed both basal levels of Cox-2 and EGF-mediated induction of Cox-2 protein and synthesis of prostaglandin E2. Retinoids also suppressed the induction of Cox-2 mRNA by EGF. Transient transfection experiments showed that EGF caused about a 100% increase in Cox-2 promoter activity, an effect that was suppressed by retinoids. Levels of epidermal growth factor receptor were unaffected by retinoids. Epidermal growth factor caused a nearly 10-fold increase in mitogen-activated protein kinase activity; this effect was not blocked by retinoids.

Original languageEnglish (US)
Pages (from-to)2890-2895
Number of pages6
JournalCancer research
Volume57
Issue number14
StatePublished - Jul 15 1997

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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