Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells

Kotha Subbaramaiah, Nitin Telang, John T. Ramonetti, Ruriko Araki, Bethany DeVito, Babette B. Weksler, Andrew J. Dannenberg

Research output: Contribution to journalArticlepeer-review

417 Scopus citations

Abstract

Cancers form more prostaglandins than the normal tissues from which they arise. Cyclooxygenase-2 (prostaglandin H synthase-2, PGHS-2, EC 1.14.99.1), an enzyme that catalyzes the formation of prostaglandins from arachidonic acid, is inducible in epithelial cells. We investigated whether transformation of mammary cells was associated with up-regulation of Cox-2 as a basis for increased production of prostaglandin E2 (PGE2) by these cells. This hypothesis was tested in two pairs of mammary cell lines between which the mode of transformation (viral versus oncogene) differed. Vitally transformed RIII/Pr1 cells, which are highly tumorigenic in mice, produced markedly increased amounts of PGE2 compared to virally initiated RIII/MG cells, a weakly tumorigenic strain. Cox-2 mRNA and protein were increased concomitantly in RIII/Pr1 cells. Similarly, Ras-induced transformation of C57/MG cells resulted in increased levels of Cox-2 mRNA and protein and increased production of PGE2. Nuclear run-offs revealed increased rates of Cox-2 transcription in the virally transformed and oncogene-transformed cell lines. Transient transfection experiments demonstrated that the oncogenes src and ras up-regulated Cox-2 promoter activity. Src-mediated up-regulation of Cox-2 promoter activity was suppressed by dominant negative ras. Our data indicate that cellular transformation is associated with enhanced transcription of Cox-2 and increased production of PGE2.

Original languageEnglish (US)
Pages (from-to)4424-4429
Number of pages6
JournalCancer research
Volume56
Issue number19
StatePublished - Oct 1 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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