COX-2 expression is induced by UVB exposure in human skin: Implications for the development of skin cancer
COX-2 expression is induced by UVB exposure in human skin: Implications for the development of skin cancer
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DOI：
10.1093/carcin/19.5.723
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发表时间：
1998-05-01
期刊：
影响因子：
4.7
通讯作者：
Pentland, AP
中科院分区：
文献类型：
--
作者：
Buckman, SY;Gresham, A;Pentland, AP
大量文献证实了紫外线照射作为肿瘤引发剂和促进剂的作用，诱导鳞状细胞癌和基底细胞癌。人类表皮是一种将花生四烯酸积极代谢为前列腺素的组织，这种代谢受到前列腺素 H 合酶（也称为环氧合酶）的作用的调节。紫外线促进活性的一种机制可能涉及其诱导前列腺素形成的能力。我们实验室的工作表明，人类角质形成细胞急性暴露于 WE 辐射会导致前列腺素 E-2 (PGE(2)) 的产生增加。当在体外用 30 mJ/cm(2) UVB 照射后检查培养的人角质形成细胞时，Western blot 分析显示 COX-2 蛋白增加了 6 倍，在照射后 6 小时明显，并在照射后 24 小时达到峰值。此外，当人类受试者在防晒皮肤上接受高达最小红斑剂量 (MED) 四倍的照射并在 24 小时后进行活检时，COX-2 蛋白的表达上调 通过免疫荧光显微镜观察到 COX-2 蛋白表达的变化，RNAase 保护测定支持了这一观察结果，表明 COX-2 信息的诱导在体外辐射后约 12 小时达到峰值。此外，通过免疫组织化学和蛋白质印迹分析，与正常未暴露在阳光下的对照皮肤相比，人鳞状细胞癌活组织检查显示 COX-2 蛋白的染色强烈增强。总之，这些数据表明 COX-2 通过 UVB 照射急剧上调，并表明需要进一步研究 COX-2 表达作为介导人类皮肤肿瘤发展的潜在药理学靶点。
Extensive documentation has validated the role of UV irradiation as a tumor initiator and promoter, inducing both squamous and basal cell carcinomas. Human epidermis is a tissue which undergoes active metabolism of arachidonic acid to prostaglandins which is regulated by the action of prostaglandin H synthase (also known as cyclooxygenase), One mechanism for the promotional activity of UV light may involve its ability to induce prostaglandin formation. Work in our laboratory has demonstrated that acute exposure of human keratinocytes to WE irradiation results in increased production of prostaglandin E-2(PGE(2)). When cultured human keratinocytes were examined after irradiation with 30 mJ/cm(2) UVB in vitro, Western blot analysis showed a 6-fold increase in COX-2 protein which was evident at 6 h and peaked 24 h after irradiation, Furthermore, when human subjects were irradiated on sun-protected skin with up to four times their minimal erythema dosage (MED) and biopsied 24 h later, upregulation of COX-2 protein expression was observed via immunofluorescence microscopy, RNAase protection assays supported this observation, showing induction of COX-2 message which peaked at similar to 12 h following irradiation in vitro. Furthermore, human squamous cell carcinoma biopsies exhibited strongly enhanced staining for COX-2 protein via immunohistochemistry and Western analysis when compared to normal non-sun-exposed control skin. Together, these data demonstrate acute upregulation of COX-2 via UVB irradiation and suggest the need for further studies of COX-2 expression as a potential pharmacological target mediating human skin tumor development.