Inhibition of cyclooxygenase-2 gene expression by p53 Academic Article Article uri icon

Overview

MeSH Major

  • Adiponectin
  • Adipose Tissue, White
  • Aromatase
  • Breast
  • C-Reactive Protein
  • Interleukin-6
  • Leptin
  • Menopause

abstract

  • Oncogenes enhance the expression of cyclooxygenase (Cox)-2, but interactions between tumor suppressor genes and Cox-2 have not been studied. In the present work, we have compared the levels of Cox-2 and the production of prostaglandin E2 in mouse embryo fibroblasts that do not express any p53 ((10)1) versus the same cell line ((10. 1)Val5) engineered to overexpress wild-type (wt) p53 at 32 degrees C or mutant p53 at 39 degrees C. Cells expressing wt p53 showed about a 10-fold decrease in synthesis of prostaglandin E2 compared with those expressing mutant p53. Levels of Cox-2 protein and mRNA were markedly suppressed by wt p53 but not by mutant p53. Nuclear run-offs revealed decreased rates of Cox-2 transcription in cells expressing wt p53. The activity of the Cox-2 promoter was reduced by 85% in cells expressing wt p53 but was reduced only by 30% in cells expressing mutant p53 compared with cells null for p53. The effect of p53 on the suppression of Cox-2 promoter activity was localized to the first 40 base pairs 5' from the transcription start site. Electrophoretic mobility shift assay revealed that p53 competed with TATA-binding protein for binding to mouse Cox-2 or human Cox-2 promoter extending from -50 to +52 base pairs. The results of this study suggest that interactions between p53 and Cox-2 could be important for understanding why levels of Cox-2 are undetectable in normal cells and increased in many tumors.

publication date

  • April 16, 1999

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1074/jbc.274.16.10911

PubMed ID

  • 10196169

Additional Document Info

start page

  • 10911

end page

  • 5

volume

  • 274

number

  • 16