Several transcription factors regulate COX-2 gene expression in pancreatic beta-cells

Mol Biol Rep. 2007 Sep;34(3):199-206. doi: 10.1007/s11033-007-9085-3. Epub 2007 May 16.

Abstract

Cyclooxygenase-2 (COX-2) expression is associated with many aspects of physiological and pathological conditions, including pancreatic beta-cell dysfunction. Prostaglandin E2 (PGE2) production, as a consequence of COX-2 gene induction, has been reported to impair beta-cell function. The molecular mechanisms involved in the regulation of COX-2 gene expression are not fully understood. In this report, we used pancreatic beta-cells (RINm5F) to explore the potential transcription factors regulating COX-2 promoter activity. Using promoter screening method, we selected several transcription factors in our study. Through luciferase reporter studies, we found that these factors can regulate COX-2 promoter activity in RINm5F cells. Among these factors, cyclic AMP response-element binding protein (CREB), Ets family members Ets-1 and Elk-1 can positively regulate COX-2 promoter activity. On the contrary, signal transducer and activator of transcription 1 (STAT1) plays a negative role on COX-2 promoter. Our findings will be helpful for better understanding the transcriptional regulation of COX-2 in pancreatic beta-cells. Moreover, these transcriptional regulators of COX-2 expression will be potential targets for the prevention of beta-cell damage mediated by PGE2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclic AMP Response Element-Binding Protein / physiology
  • Cyclooxygenase 2 / genetics*
  • Gene Expression Regulation, Enzymologic*
  • Insulin-Secreting Cells / enzymology*
  • Insulin-Secreting Cells / metabolism
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Protein c-ets-1 / physiology
  • Rats
  • STAT1 Transcription Factor / physiology
  • Transcription Factors / metabolism
  • Transcription Factors / physiology*
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • ets-Domain Protein Elk-1 / physiology

Substances

  • Cyclic AMP Response Element-Binding Protein
  • Ets1 protein, rat
  • Proto-Oncogene Protein c-ets-1
  • STAT1 Transcription Factor
  • Stat1 protein, rat
  • Transcription Factors
  • ets-Domain Protein Elk-1
  • Cyclooxygenase 2