PEA3 Is Up-regulated in Response to Wnt1 and Activates the Expression of Cyclooxygenase-2 Academic Article uri icon

Overview

MeSH Major

  • Gene Expression Regulation, Enzymologic
  • Isoenzymes
  • Prostaglandin-Endoperoxide Synthases
  • Proto-Oncogene Proteins
  • Transcription Factors
  • Up-Regulation
  • Zebrafish Proteins

abstract

  • The inducible prostaglandin synthase cyclooxygenase-2 (COX-2) is aberrantly expressed in intestinal tumors resulting from APC mutation, and is also transcriptionally up-regulated in mouse mammary epithelial cells in response to Wnt1 expression. beta-Catenin stabilization is a consequence of both APC mutation and Wnt signaling. We have previously observed coordinate regulation of the matrilysin promoter by beta-catenin and Ets family transcription factors of the PEA3 subfamily. Here we show that while beta-catenin only weakly activates the COX-2 promoter, PEA3 family transcription factors are potent activators of COX-2 transcription. Consistent with this, PEA3 is up-regulated in Wnt1-expressing mouse mammary epithelial cells, and PEA3 factors are highly expressed in tumors from Wnt1 transgenic mice, in which Cox-2 is also up-regulated. Promoter mapping experiments suggest that the NF-IL6 site in the COX-2 promoter is important for mediating PEA3 responsiveness. The NF-IL6 site is also important for COX-2 transcription in some colorectal cancer lines (Shao, J., Sheng, H., Inoue, H., Morrow, J. D., and DuBois, R. N. (2000) J. Biol. Chem. 275, 33951-33956), and PEA3 factors are highly expressed in colorectal cancer cell lines. Therefore, we speculate that PEA3 factors may contribute to the up-regulation of COX-2 expression resulting from both APC mutation and Wnt1 expression.

publication date

  • June 8, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1074/jbc.M010692200

PubMed ID

  • 11274170

Additional Document Info

start page

  • 20108

end page

  • 15

volume

  • 276

number

  • 23