PMID:10987272

Citation	Chulada, PC, Thompson, MB, Mahler, JF, Doyle, CM, Gaul, BW, Lee, C, Tiano, HF, Morham, SG, Smithies, O and Langenbach, R (2000) Genetic disruption of Ptgs-1, as well as Ptgs-2, reduces intestinal tumorigenesis in Min mice. Cancer Res. 60:4705-8
Abstract	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.
Links	PubMed
Keywords	Animals; Crosses, Genetic; Cyclooxygenase 1; Cyclooxygenase 2; Dinoprostone/biosynthesis; Female; Intestinal Neoplasms/enzymology; Intestinal Neoplasms/genetics; Intestinal Neoplasms/prevention & control; Intestinal Polyps/enzymology; Intestinal Polyps/genetics; Intestinal Polyps/prevention & control; Intestines/enzymology; Isoenzymes/deficiency; Isoenzymes/genetics; Male; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Prostaglandin-Endoperoxide Synthases/deficiency; Prostaglandin-Endoperoxide Synthases/genetics; Reference Values
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