Genetic Disruption of Ptgs-1, as well as of Ptgs-2, Reduces Intestinal Tumorigenesis in Min Mice
PC Chulada, MB Thompson, JF Mahler, CM Doyle… - Cancer research, 2000 - AACR
PC Chulada, MB Thompson, JF Mahler, CM Doyle, BW Gaul, C Lee, HF Tiano, SG Morham…
Cancer research, 2000•AACRTwo 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∼ 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 …
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∼ 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 …
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 ∼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.
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