Genetic disruption of Ptgs-1, as well as of Ptgs-2, reduces intestinal tumorigenesis in Min mice

Two isoforms of cyclooxygenase (COX) are known, and to date most studies ha ve implicated COX-2, rather than COX-1, as the isoform involved in colon ca rcinogenesis. In the present study, we show that homologous disruption of e ither Ptgs-1 or Ptgs-2 (genes coding for COX-1 or COX-2, respectively) redu ced polyp formation in Min/+ mice by similar to 80%, Only COX-1 protein was immunohistochemically detected in normal intestinal tissue, whereas both C OX-1 and variable levels of COX-2 protein were detected in polyps. Prostagl andin E-2 was increased in polyps compared with normal tissue, and both COX -1 and COX-2 contributed to the PGE(2) produced. The results indicate that COX-1, as well as COX-2, plays a key role in intestinal tumorigenesis and t hat COX-1 may also be a chemotherapeutic target for nonsteroidal anti-infla mmatory drugs.