Detection of differentially expressed genes in human colon carcinoma cells treated with a selective COX-2 inhibitor.
Numerous reports suggest that use of nonsteroidal anti-inflammatory drugs (NSAIDs) decrease mortality from colorectal cancer. To better understand all of the mechanisms underlying this effect, the global pattern of gene expression in colon carcinoma cells following treatment with NS-398, a selective cyclo-oxygenase-2 inhibitor was evaluated. We utilized suppression subtractive hybridization combined with differential screening to identify genes whose expression was affected following treatment. Among the subtracted cDNA fragments confirmed as differentially expressed, there were two which are known to be involved in the regulation of cell adhesion (human FAT and proto-cadherin-7). We identified two other genes whose levels were decreased and these are known to be involved in the regulation of cell proliferation (cyclin K and p-100). We identified additional genes which are involved in different signaling pathways which regulate programmed cell death (Dynamin 2, Pdcd4 and LIP.1). These results provide evidence that some of the effects of NS-398 on carcinoma cells may be due to modulation of genes which regulate programmed cell death, cell proliferation and cell-cell communication. Additional studies are underway to determine the biological function of the novel genes that were identified.
Zhang
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Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232-2279, USA.
DuBois
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D048868:Adaptor Proteins, Signal Transducing; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins; D015152:Blotting, Northern; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics; D051177:Catenins; D002448:Cell Adhesion; D003110:Colonic Neoplasms / Q000235:genetics*; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D018076:DNA, Complementary / Q000235:genetics; D034284:Dynamin I; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D009578:Nitrobenzenes / Q000494:pharmacology*; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D000091363:Protocadherins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D016601:RNA-Binding Proteins; D012004:Rectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000235:genetics; D013379:Substrate Specificity; D013382:Subtraction Technique; D013449:Sulfonamides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D000095002:Delta Catenin
D048868:Adaptor Proteins, Signal Transducing; D000894:Anti-Inflammatory Agents, Non-Steroidal; D051017:Apoptosis Regulatory Proteins; C113028:CCNK protein, human; D015820:Cadherins; D002352:Carrier Proteins; D051177:Catenins; D016213:Cyclins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D018076:DNA, Complementary; C502403:FAT1 protein, human; D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009578:Nitrobenzenes; C113391:PCDH7 protein, human; C114487:PDCD4 protein, human; C094398:PPFIA1 protein, human; D010750:Phosphoproteins; D011506:Proteins; D000091363:Protocadherins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D016601:RNA-Binding Proteins; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D034284:Dynamin I; D020558:GTP Phosphohydrolases; D034281:Dynamins; D000095002:Delta Catenin