Alterations in Cellular Adhesion and Apoptosis in Epithelial Cells Overexpressing Prostaglandin Endoperoxide Synthase 2

Cell. 1995 Nov 3;83(3):493-501. doi: 10.1016/0092-8674(95)90127-2.

Abstract

Prostaglandin endoperoxide synthase 2, also referred to as cyclooxygenase 2 (COX-2), is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. Rat intestinal epithelial (RIE) cells were permanently transfected with a COX-2 expression vector oriented in the sense (RIE-S) or antisense (RIE-AS) direction. The RIE-S cells expressed elevated COX-2 protein levels and demonstrated increased adhesion to extracellular matrix (ECM) proteins. E-cadherin was undetectable in RIE-S cells, but was elevated in parental RIE (RIE-P) and RIE-AS cells. RIE-S cells were resistant to butyrate-induced apoptosis, had elevated BCL2 protein expression, and reduced transforming growth factor beta 2 receptor levels. The phenotypic changes involving both increased adhesion to ECM and inhibition of apoptosis were reversed by sulindac sulfide (a COX inhibitor). These studies demonstrate that overexpression of COX-2 leads to phenotypic changes in intestinal epithelial cells that could enhance their tumorigenic potential.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkaline Phosphatase / metabolism
  • Animals
  • Apoptosis / physiology
  • Cadherins / metabolism
  • Cell Adhesion / physiology
  • Epithelium / enzymology
  • Extracellular Matrix / metabolism
  • Gene Expression / physiology
  • Intestines / cytology*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • Protein Binding / physiology
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2
  • Rats
  • Receptors, Transforming Growth Factor beta / metabolism

Substances

  • Cadherins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Receptors, Transforming Growth Factor beta
  • Prostaglandin-Endoperoxide Synthases
  • Protein-Tyrosine Kinases
  • Alkaline Phosphatase