The association between a mutated ras gene and cyclooxygenase-2 expression in human breast cancer cell lines.
Cyclooxygenase (COX) is rate-limiting for arachidonic acid metabolism to the prostanoid family of eicosanoids. Some human breast cancers, notably those which are estrogen receptor (ER)-negative with high metastatic potential, produce high levels of prostaglandin E2 (PGE2). In some cell types, expression of the inducible COX-2 isoform occurred in association with a ras gene mutation. We determined COX-1 and COX-2 expression, and the corresponding PGE2 secretions, in 4 ER-negative human breast cancer cell lines, the MCF10A breast epithelial cell line, and the same non-cancerous line transfected with a mutated ras gene. The highly invasive MDA-MB-231 and Hs578T cancer cell lines, which possess a mutated Ki-ras and H-ras, respectively, expressed constitutive and inducible COX-2, and produced high PGE2 levels; the less invasive MDA-MB-435 and SK-BR-3 lines, without a mutated ras, possessed only low levels of COX-2, and secreted correspondingly low PGE2 levels. Similarly, the ras transfectant, but not parental MCF10A cells, expressed inducible COX-2. Chemosuppression with a selective COX-2 inhibitor may be effective only in that minority of breast cancers which have a mutated ras gene.
Division of Nutrition and Endocrinology, American Health Foundation, Valhalla, NY 10595, USA.
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Gilhooly
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Rose
D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D002296:Carcinosarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D011905:Genes, ras; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008565:Membrane Proteins; D009154:Mutation; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000032:analysis; D014407:Tumor Cells, Cultured
D007527:Isoenzymes; D008565:Membrane Proteins; D011960:Receptors, Estrogen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases