Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2.
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.
Department of Medicine, Vanderbilt University Medical Center, Veterans Affairs Medical Center, Nashville, Tennessee 37232, USA.
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D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D004848:Epithelium / Q000201:enzymology; D005109:Extracellular Matrix / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D007422:Intestines / Q000166:cytology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D051381:Rats; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism
D015820:Cadherins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D018125:Receptors, Transforming Growth Factor beta; D011451:Prostaglandin-Endoperoxide Synthases; D011505:Protein-Tyrosine Kinases; D000469:Alkaline Phosphatase