Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells
Benzo[a]pyrene up-regulates cyclooxygenase-2 gene expression in oral epithelial cells
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DOI：
10.1093/carcin/18.4.795
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发表时间：
1997-04-01
期刊：
影响因子：
4.7
通讯作者：
Dannenberg, AJ
中科院分区：
文献类型：
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作者：
Kelley, DJ;Mestre, JR;Dannenberg, AJ
环氧合酶可能在吸烟相关癌症的发病机制中起重要作用，因为它激活致癌物并催化前列腺素的生物合成。我们研究了烟草烟雾中的多环芳烃苯并[a]芘(B[a]P)对正常和转化的口腔上皮细胞环氧合酶-2(COX-2)基因、蛋白和前列腺素E(2)(PGE(2))合成的影响。苯并[a]P对PGE(2)的产生呈剂量依赖性增加，最大增幅接近100%。PGE(2)合成增强与COX-2蛋白含量增加有关。B[a]P还导致正常细胞和转化细胞中COX-2mRNA的表达增加了一倍。用COX-2启动子构建的瞬时转染法显示，B[a]P介导的COX-2mRNA的诱导反映了转录的增加，COX-1的水平不受B[a]P的影响，B[e]P不影响PGE(2)的合成或COX-a的量，这些数据是重要的，因为B[a]P介导的COX-2的诱导可能通过促进诱变剂的产生和前列腺素的合成而易于致癌。
Cyclooxygenase may be important in the pathogenesis of smoking-related cancer because it activates carcinogens and catalyzes prostaglandin biosynthesis. We determined the effects of benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon in tobacco smoke, on cyclooxygenase-2 (Cox-2) mRNA, protein and synthesis of prostaglandin E(2) (PGE(2)) in normal and transformed oral epithelial cells. Treatment with B[a]P caused a dose-dependent increase in production of PGE(2), with a maximal increase of similar to 100%. Enhanced synthesis of PGE(2) was associated with increased amounts of Cox-2 protein. B[a]P also caused a two-fold increase in Cox-2 mRNA in both normal and transformed cells. Transient transfections with a Cox-2 promoter construct showed that B[a]P-mediated induction of Cox-2 mRNA reflected increased transcription, Levels of Cox-1 were unaffected by B[a]P, B[e]P did not affect the synthesis of PGE(2) or amounts of Cox-a, These data are important because B[a]P-mediated induction of Cox-2 may predispose to carcinogenesis by enhancing the production of mutagens and the synthesis of prostaglandins.