TY - JOUR
T1 - The role of cyclooxygenases in inflammation, cancer, and development
AU - Williams, Christopher S.
AU - Mann, Moss
AU - DuBois, Raymond N.
N1 - Funding Information:
This work was supported in part from United States Public Health Services Grants (to RN DuBois) DK 47297, P030 ES-00267-29, PO1CA-77839. RN DuBois is a recipient of a VA Research Merit Grant and the Mina C Wallace Professor of Gastroenterology and Cancer Prevention. We also thank the TJ Martell Foundation for generous support. We thank Brigid Hogan for her insightful suggestions.
PY - 1999/12/20
Y1 - 1999/12/20
N2 - The cyclooxygenase (COX) enzymes catalyze a key step in the conversion of arachidonate to PGH2, the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases. Prostaglandins play critical roles in numerous biologic processes, including the regulation of immune function, kidney development, reproductive biology, and gastrointestinal integrity. There are two COX isoforms, which differ mainly in their pattern of expression. COX-1 is expressed in most tissues, whereas COX-2 usually is absent, but is induced by numerous physiologic stimuli. Surprisingly, disruption of Cox1 (Ptgs1) in the mouse did not result in gastrointestinal abnormalities. cox-2 (Ptgs2) null mice show reproductive anomalies and defects in kidney development. Epidemiologic, animal, and human data indicate that NSAIDs, inhibitors of cyclooxygenase, are chemopreventive for colon cancer. COX-2 is overexpressed in 50 of benign polyps and 80-85 of adenocarcinomas. Offspring from cox-2 null by Apc(Δ716) matings exhibit an 86 reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth. The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/or immune function.
AB - The cyclooxygenase (COX) enzymes catalyze a key step in the conversion of arachidonate to PGH2, the immediate substrate for a series of cell specific prostaglandin and thromboxane synthases. Prostaglandins play critical roles in numerous biologic processes, including the regulation of immune function, kidney development, reproductive biology, and gastrointestinal integrity. There are two COX isoforms, which differ mainly in their pattern of expression. COX-1 is expressed in most tissues, whereas COX-2 usually is absent, but is induced by numerous physiologic stimuli. Surprisingly, disruption of Cox1 (Ptgs1) in the mouse did not result in gastrointestinal abnormalities. cox-2 (Ptgs2) null mice show reproductive anomalies and defects in kidney development. Epidemiologic, animal, and human data indicate that NSAIDs, inhibitors of cyclooxygenase, are chemopreventive for colon cancer. COX-2 is overexpressed in 50 of benign polyps and 80-85 of adenocarcinomas. Offspring from cox-2 null by Apc(Δ716) matings exhibit an 86 reduction in polyp number when compared to offspring from control animals, thus providing genetic evidence that COX-2 contributes to tumor formation or growth. The in vivo mechanism by which COX-2 affects tumor growth has not been determined. It is possible that both tumor and stromally derived COX-2 could influence tumor angiogenesis and/or immune function.
KW - Cancer
KW - Cyclooxygenase
KW - Development
KW - Inflammation
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U2 - 10.1038/sj.onc.1203286
DO - 10.1038/sj.onc.1203286
M3 - Review article
C2 - 10630643
AN - SCOPUS:0033590207
SN - 0950-9232
VL - 18
SP - 7908
EP - 7916
JO - Oncogene
JF - Oncogene
IS - 55
ER -