Up-regulation of cyclooxygenase-2 by product-prostaglandin E2.
The development of prostate cancer has been linked to high level of dietary fat intake. Our laboratory investigates the connection between cancer cell growth and fatty acid products. Studying human prostatic carcinoma PC-3 cells, we found that prostaglandin E2 (PGE2) increased cell growth and up-regulated the gene expression of its own synthesizing enzyme, cyclooxygenase-2 (COX-2). PGE2 increased COX-2 mRNA expression dose-dependently with the highest levels of stimulation seen at the 3-hour period following PGE2 addition. The NSAID flurbiprofen (5 microM), in the presence of exogenous PGE2, inhibited the up-regulation of COX-2 mRNA and cell growth. These data suggest that the levels of local intracellular PGE2 play a major role in the growth of prostate cancer cells through an activation of COX-2 gene expression.
Tjandrawinata
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Department of Medicine, University of California-San Francisco, USA.
Hughes-Fulford
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D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D002277:Carcinoma / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D002471:Cell Transformation, Neoplastic; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004041:Dietary Fats / Q000009:adverse effects; D015232:Dinoprostone / Q000494:pharmacology / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D005246:Feedback; D005480:Flurbiprofen / Q000494:pharmacology; D017781:Genes, Immediate-Early / Q000187:drug effects; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D008565:Membrane Proteins; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000302:isolation & purification; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004041:Dietary Fats; D007527:Isoenzymes; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005480:Flurbiprofen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone