Cyclooxygenase-2 is overexpressed in human cervical cancer

Multiple lines of evidence suggest that cyclooxygenase-2 (COX-2) is an impo rtant target for preventing epithelial malignancies. Little is known, howev er, about the expression of COX-2 in gynecological malignancies. By immunob lot analysis, COX-2 was detected in 12 of 13 cases of cervical cancer but w as undetectable in normal cervical tissue. Immunohistochemistry revealed CO X-2 in malignant epithelial cells. COX-2 was also expressed in cervical int raepithelial neoplasia, The mechanism by which COX-2 is up-regulated in cer vical 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 wi th EGF markedly induced COX-2 protein, COX-2 mRNA, and stimulated COX-2 pro moter activity, The induction of COX-2 by EGF was suppressed by inhibitors of tyrosine kinase activity, phosphatidylinositol 3-kinase, mitogen-activat ed protein kinase kinase, and p38 mitogen-activated protein kinase, Moreove r, overexpressing dominant-negative forms of extracellular signal-regulated kinase 1, c-Jun NH2-terminal kinase, p38, and c-Jun blocked EGF-mediated i nduction of COX-2 promoter activity. Taken together, these findings suggest that deregulation of the EGF receptor signaling pathway may lead to enhanc ed COX-2 expression in cervical cancer.