Reduced expression of cyclooxygenase 2 proteins in hereditary nonpolyposis colorectal cancers relative to sporadic cancers
| Autor: | Karen R. Cleary, Lixuan Xi, Patrick M. Lynch, Michael G. Lemoine, Yu Shen, Marsha L. Frazier, Frank A. Sinicrope |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
congenital
hereditary and neonatal diseases and abnormalities Pathology medicine.medical_specialty Amsterdam criteria Colorectal cancer Blotting Western medicine.disease_cause Familial adenomatous polyposis Prostaglandin-endoperoxide synthase 2 chemistry.chemical_compound Tumor Cells Cultured Humans Medicine Cyclooxygenase Inhibitors neoplasms Mutation Cyclooxygenase 2 Inhibitors Hepatology biology business.industry Gastroenterology Membrane Proteins medicine.disease Colorectal Neoplasms Hereditary Nonpolyposis Immunohistochemistry digestive system diseases Isoenzymes Blot Adenomatous Polyposis Coli chemistry Cyclooxygenase 2 Prostaglandin-Endoperoxide Synthases Cancer research biology.protein Cyclooxygenase business Receptors Transforming Growth Factor beta |
| Zdroj: | Gastroenterology. 117:350-358 |
| ISSN: | 0016-5085 |
| DOI: | 10.1053/gast.1999.0029900350 |
| Popis: | Background & Aims: Cyclooxygenase (COX) enzymes catalyze the conversion of arachidonic acid to prostaglandins. Evidence suggests that nonsteroidal anti-inflammatory drugs reduce the risk of colorectal cancer (CRC) and that this effect is mediated through COX inhibition. We analyzed and compared expression of the inducible COX-2 isoform in colorectal neoplasms from patients with hereditary nonpolyposis colorectal cancer (HNPCC), familial adenomatous polyposis (FAP), and sporadic CRC. Given that COX-2 is induced by transforming growth factor (TGF)-β and that TGF-β type II receptor ( RII ) mutations are found in HNPCCs, we determined the relationship between RII status and COX-2 expression. Methods: COX-2 protein expression was determined in colorectal epithelia using immunohistochemistry and Western blotting. Patients with HNPCC had known mutations in hMLH1 or hMSH2 genes and/or met the Amsterdam criteria. In CRCs from HNPCC cases, mutations were sought in the coding region of the RII gene using the polymerase chain reaction. Results: COX-2 was detected in adenomas from 2 of 3 HNPCC, 6 of 7 FAP, and 5 of 8 sporadic cases. In CRCs, COX-2 staining was found in 16 of 24 (67 %) HNPCC vs. 24 of 26 (92%) sporadic cases ( P = 0.035) and in 2 of 2 FAP cases. Staining intensity was reduced in HNPCCs compared with sporadic CRCs ( P = 0.035). Staining localized to the cytoplasm of neoplastic cells; normal epithelial cells were negative for COX-2. Overexpression of COX-2 in CRCs relative to normal mucosa was confirmed by Western blotting. TGF-β RII mutations were detected in 12 of 14 HNPCCs examined, including 3 of 4 COX-2–negative and 9 of 10 COX-2–positive cancers. Conclusions: The frequency and intensity of COX-2 expression was significantly reduced in HNPCCs relative to sporadic CRCs, and was not a consequence of RII mutations. Given that many HNPCCs express COX-2, inhibition of this enzyme may be an important strategy to prevent CRC in these patients. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|