Regulation of constitutive cyclooxygenase-2 expression in colon carcinoma cells

Cyclooxygenase-2 (COX-2) is not normally expressed in the human large intes tine, but its levels are increased in the majority of human colorectal carc inomas, Here we investigate the regulation of constitutive COX-2 expression and prostaglandin production in human colorectal carcinoma cells. Both COX -2 mRNA and protein were expressed in well differentiated HCA-7, Moser, LS- 174, and HT-29 cells, albeit at different levels. COX-2 expression was not detected in several poorly differentiated colon cancer cell lines including DLD-1, Transcriptional regulation played a key role for the expression of COX-2 in human colon carcinoma cells, and both the nuclear factor for inter leukin-6 regulatory element and the cAMP-response element were responsible for regulation of COX-2 transcription. COX-2 mRNA was more stable in HCA-7 cells than in the other cell lines tested. Both transcriptional and post-tr anscriptional regulation of COX-2 involved the MAP kinase pathway. Modulati on of the Akt/protein kinase B or Rho B signaling pathways altered the leve ls of COX-2 expression. Furthermore, COX-2 protein is degraded through ubiq uitin proteolysis, and its half-life was similar to3.5-8 h, HCA-7 cells pro duced significant quantities of prostaglandin E-2 and other prostaglandins. Moser and LS-174 cells also generated prostaglandins, but levels were sign ificantly lower than that observed in HCA-7 cells.