Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice.
Two isoforms of cyclooxygenase (COX) are known, and to date most studies have implicated COX-2, rather than COX-1, as the isoform involved in colon carcinogenesis. In the present study, we show that homologous disruption of either Ptgs-1 or Ptgs-2 (genes coding for COX-1 or COX-2, respectively) reduced polyp formation in Min/+ mice by approximately 80%. Only COX-1 protein was immunohistochemically detected in normal intestinal tissue, whereas both COX-1 and variable levels of COX-2 protein were detected in polyps. Prostaglandin E2 was increased in polyps compared with normal tissue, and both COX-1 and COX-2 contributed to the PGE2 produced. The results indicate that COX-1, as well as COX-2, plays a key role in intestinal tumorigenesis and that COX-1 may also be a chemotherapeutic target for nonsteroidal anti-inflammatory drugs.
Pubmed ID: 10987272 RIS Download
Animals | Crosses, Genetic | Cyclooxygenase 1 | Cyclooxygenase 2 | Dinoprostone | Female | Intestinal Neoplasms | Intestinal Polyps | Intestines | Isoenzymes | Male | Membrane Proteins | Mice | Mice, Inbred C57BL | Mice, Knockout | Prostaglandin-Endoperoxide Synthases | Reference Values