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.
Chulada
P C
PC
Laboratory of Experimental Carcinogenesis and Mutagenesis, NIH, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA. chulada@niehs.nih.gov
Thompson
M B
MB
Mahler
J F
JF
Doyle
C M
CM
Gaul
B W
BW
Lee
C
C
Tiano
H F
HF
Morham
S G
SG
Smithies
O
O
Langenbach
R
R
D000818:Animals; D003433:Crosses, Genetic; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D005260:Female; D007414:Intestinal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control*; D007417:Intestinal Polyps / Q000201:enzymology* / Q000235:genetics / Q000517:prevention & control*; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011451:Prostaglandin-Endoperoxide Synthases / Q000172:deficiency / Q000235:genetics*; D012016:Reference Values
D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; C496512:Ptgs1 protein, mouse; D015232:Dinoprostone