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PGE2 Production in Oral Cancer Cell Lines is COX-2-dependentLaboratory for Mucosal Immunology (LMI), Department of Oral Biology, University of Oslo, P.b. 1052, Blindern, Oslo 0316, Norway Correspondence: thalsten{at}odont.uio.no It has been suggested that epithelial cyclooxyge-nase-2 (COX-2) promotes oral carcinogenesis and carcinoma malignancy through increased prostaglandin E2 (PGE2) production. Although oral squamous cell carcinomas (OSCC) often express COX-2, they may also produce PGE2 in a COX-1-dependent manner. We used 6 isolated cell lines to investigate which COX isoforms OSCC may use for PGE2 production. COX-1 and -2 expression patterns divided the 6 OSCC cell lines into 3 distinct groups: both COX isoforms low, only COX-1 high, or both COX isoforms high. Multicolor immunohistofluorescence staining confirmed the COX-expression profiles in organotypic 3D cultures and the COX-2 dominance in OSCC tumors. Epidermal growth factor (EGF) stimulation induced COX-2 (but not COX-1) expression and increased PGE2 production, which was attenuated by COX-2 (but not COX-1) specific inhibition or siRNA-mediated COX-2 gene knockdown. Thus, PGE2 production in OSCC cell lines was COX-2-dependent.
Key Words: oral squamous cell carcinoma siRNA prostaglandin E2 immunohistofluorescence Abbreviations: COX, cyclooxygenase EGF, epidermal growth factor EGFR, epidermal growth factor receptor NSAID, non-steroidal anti-inflammatory drug OSCC, oral squamous cell carcinoma PG, prostaglandin PGE2, prostaglandin E2 PGES, prostaglandin E2 synthase.
Journal of Dental Research, Vol. 88, No. 2,
164-169 (2009) |
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