Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells.
Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells.
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发表时间：
1997-07
期刊：
影响因子：
11.2
通讯作者：
J. Mestre;K. Subbaramaiah;P. Sacks;S. Schantz;T. Tanabe;H. Inoue;A. Dannenberg
中科院分区：
文献类型：
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作者：
J. Mestre;K. Subbaramaiah;P. Sacks;S. Schantz;T. Tanabe;H. Inoue;A. Dannenberg
环氧合酶-2(COX-2)是环氧合酶的诱导形式，在肿瘤和转化细胞中表达上调。由于这种酶催化花生四烯酸形成前列腺素，抑制其表达的化学预防策略可能对预防癌症有用。我们研究了维甲酸是否抑制了口腔鳞癌细胞中COX-2的基础表达或EGF介导的COX-2的诱导。维甲酸[全反式维甲酸、9-顺式-维甲酸、13-顺式-维甲酸和维甲酸乙酯]可抑制COX-2和EGF诱导的COX-2蛋白和前列腺素E2的合成。维甲酸还可抑制EGF对COX-2mRNA的诱导。瞬时转染实验表明，EGF可使COX-2启动子活性增加约100%，这种作用可被维甲酸抑制。表皮生长因子受体的水平不受维甲酸的影响。表皮生长因子导致丝裂原活化蛋白激酶活性增加近10倍；这一作用不被维甲酸阻断。
Cyclooxygenase-2 (Cox-2), the inducible form of cyclooxygenase, is up-regulated in tumors and transformed cells. Because this enzyme catalyzes the formation of prostaglandins from arachidonic acid, chemopreventive strategies that suppress its expression could be useful for preventing cancer. We investigated whether retinoids suppressed basal expression of Cox-2 or EGF-mediated induction of Cox-2 in human oral squamous carcinoma cells. Treatment with retinoids [all-trans-retinoic acid (all-trans-RA), 9-cis-RA, 13-cis-RA, and retinyl acetate] suppressed both basal levels of Cox-2 and EGF-mediated induction of Cox-2 protein and synthesis of prostaglandin E2. Retinoids also suppressed the induction of Cox-2 mRNA by EGF. Transient transfection experiments showed that EGF caused about a 100% increase in Cox-2 promoter activity, an effect that was suppressed by retinoids. Levels of epidermal growth factor receptor were unaffected by retinoids. Epidermal growth factor caused a nearly 10-fold increase in mitogen-activated protein kinase activity; this effect was not blocked by retinoids.