Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells Academic Article uri icon

Overview

MeSH Major

  • Cell Transformation, Neoplastic
  • Dinoprostone
  • Gene Expression Regulation, Neoplastic
  • Isoenzymes
  • Mammary Glands, Animal
  • Neoplasm Proteins
  • Prostaglandin-Endoperoxide Synthases
  • Transcription, Genetic

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. Virally 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.

publication date

  • October 1996

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed ID

  • 8813136

Additional Document Info

start page

  • 4424

end page

  • 9

volume

  • 56

number

  • 19