Cyclooxygenase-2 is overexpressed in human cervical cancer.
Cyclooxygenase-2 is overexpressed in human cervical cancer.
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发表时间：
2001-02
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通讯作者：
Swati Kulkarni;J. Rader;Fan Zhang;H. Liapis;A. Koki;J. Masferrer;K. Subbaramaiah;A. Dannenberg
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作者：
Swati Kulkarni;J. Rader;Fan Zhang;H. Liapis;A. Koki;J. Masferrer;K. Subbaramaiah;A. Dannenberg
多种证据表明，环氧合酶-2（考克斯-2）是预防上皮恶性肿瘤的重要靶点。然而，关于考克斯-2在妇科恶性肿瘤中的表达知之甚少。免疫印迹法检测考克斯-2在13例宫颈癌中12例阳性，而在正常宫颈组织中均阴性。免疫组化显示考克斯-2在恶性上皮细胞中表达。考克斯-2在宫颈上皮内瘤变中也有表达。宫颈癌中考克斯-2上调的机制尚不清楚。由于表皮生长因子（EGF）受体在宫颈癌中普遍过表达，我们研究了EGF是否可以诱导培养的人宫颈癌细胞中的考克斯-2。EGF处理显著诱导考克斯-2蛋白、考克斯-2 mRNA表达，并刺激考克斯-2启动子活性。EGF对考克斯-2的诱导作用可被酪氨酸激酶活性抑制剂、磷脂酰肌醇3-激酶、有丝分裂原活化蛋白激酶和p38有丝分裂原活化蛋白激酶抑制剂抑制。此外，过表达显性负性形式的细胞外信号调节激酶1、c-Jun NH 2末端激酶、p38和c-Jun可阻断EGF介导的考克斯-2启动子活性诱导。综上所述，这些研究结果表明，EGF受体信号通路的失调可能导致宫颈癌中考克斯-2表达增强。
Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) is an important target for preventing epithelial malignancies. Little is known, however, about the expression of COX-2 in gynecological malignancies. By immunoblot analysis, COX-2 was detected in 12 of 13 cases of cervical cancer but was undetectable in normal cervical tissue. Immunohistochemistry revealed COX-2 in malignant epithelial cells. COX-2 was also expressed in cervical intraepithelial neoplasia. The mechanism by which COX-2 is up-regulated in cervical cancer is unknown. Because the epidermal growth factor (EGF) receptor is commonly overexpressed in cervical cancer, we investigated whether EGF could induce COX-2 in cultured human cervical carcinoma cells. Treatment with EGF markedly induced COX-2 protein, COX-2 mRNA, and stimulated COX-2 promoter activity. The induction of COX-2 by EGF was suppressed by inhibitors of tyrosine kinase activity, phosphatidylinositol 3-kinase, mitogen-activated protein kinase kinase, and p38 mitogen-activated protein kinase. Moreover, overexpressing dominant-negative forms of extracellular signal-regulated kinase 1, c-Jun NH2-terminal kinase, p38, and c-Jun blocked EGF-mediated induction of COX-2 promoter activity. Taken together, these findings suggest that deregulation of the EGF receptor signaling pathway may lead to enhanced COX-2 expression in cervical cancer.