文章：

通过靶向紫外线B光信号预防非黑色素瘤皮肤癌

Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling

原文发布日期：2004-01-01

DOI: 10.1038/nrc1253

类型: Review Article

开放获取: 否

要点：

1. The incidence of non-melanoma skin cancers such as squamous-cell carcinoma (SCC) in many countries including the United States has been increasing recently with significant effects on public health. Primary prevention — for example, the use of sun screens — has proven inadequate in impacting the incidence of skin cancer, and this has stimulated the development of chemoprevention strategies.
2. Ultraviolet B (UVB) light acts as a tumour-initiating, -promoting and -progressing agent in the generation of SCC.
3. UVB light mediates skin-tumour promotion through activation of the transcription factor complex activator protein-1 (AP-1) and through the expression of the cyclooxygenase-2 (COX2) gene.
4. UVB light mediates AP-1 activation, which increases binding of the differentially phosphorylated cyclic-AMP-response-element-binding protein (CREB) to the CRE site and c-FOS AP-1 site within the promoter region of the c-FOS gene, so increasing transcription and expression of c-FOS.
5. UVB light mediates COX2 transcription through increased binding of differentially phosphorylated CREB to a CRE site in the promoter region of the COX2 gene.
6. UVB light induces increased phosphorylation of CREB at serine 133 through activation of p38 mitogen-activated protein kinase (MAPK), which results in increased transcription of the c-FOS and COX2 genes.
7. UVB light decreases phosphorylation of CREB at Ser129 through activation of the phosphatidylinositol 3-kinase (PI3K)–AKT pathway, which results in increased binding of CREB to the promoter regions of the c-FOS and COX2 genes and increased transcription.
8. Epigallocatechin gallate (EGCG) is an inhibitor of the UVB-light-induced p38 MAPK pathway and has shown chemopreventive activity in preventing UVB-light-induced skin-tumour development.
9. Nordihydroguaiaretic acid (NDGA) is an inhibitor of UVB-light-induced PI3K–AKT pathway and NDGA has been shown to have chemopreventive activity.
10. New chemopreventive agents that target UVB-light signalling pathways — leading to AP-1 activation and COX2 expression — are being translated into the clinic.

要点翻译：

1. 包括美国在内的许多国家，非黑色素瘤皮肤癌（如鳞状细胞癌）的发病率近年来持续上升，对公众健康造成显著影响。初级预防措施（如使用防晒霜）已被证明不足以降低皮肤癌发病率，这促进了化学预防策略的发展。
2. 紫外线B（UVB）在鳞状细胞癌的发生过程中扮演着肿瘤起始、促进和进展的角色。
3. UVB通过激活转录因子复合物激活蛋白1（AP-1）和诱导环氧合酶2（COX2）基因表达介导皮肤肿瘤促进。
4. 其介导的AP-1激活会增强差异磷酸化环磷腺苷效应元件结合蛋白（CREB）与c-FOS基因启动子区域内CRE位点及c-FOS AP-1位点的结合，从而提升c-FOS的转录与表达。
5. UVB通过增强差异磷酸化CREB与COX2基因启动子区CRE位点的结合来介导COX2转录。
6. 它通过激活p38丝裂原活化蛋白激酶（MAPK）诱导CREB丝氨酸133位点磷酸化增强，进而促进c-FOS和COX2基因转录。
7. 同时，UVB通过激活磷脂酰肌醇3-激酶（PI3K）-AKT通路降低CREB丝氨酸129位点磷酸化，这增强了CREB与c-FOS和COX2基因启动子区域的结合并提升转录水平。
8. 表没食子儿茶素没食子酸酯（EGCG）是UVB诱导的p38 MAPK通路抑制剂，在预防UVB诱导的皮肤肿瘤发展方面显示出化学预防活性。
9. 去甲二氢愈创木酸（NDGA）作为UVB诱导的PI3K-AKT通路抑制剂，同样被证实具有化学预防作用。
10. 目前，针对UVB信号通路（导致AP-1激活和COX2表达）的新型化学预防剂正在向临床转化。

英文摘要：

The incidence of non-melanoma skin cancer is rising and primary prevention, including the use of sun screens, has proven inadequate in reducing this incidence. Chemoprevention strategies are therefore needed. Ultraviolet B light can initiate skin-tumour development through DNA damage and mutation in crucial target genes, and can also promote the clonal expansion of initiated cells to give rise to benign skin tumours. Targeting key molecules in the ultraviolet-light signal-transduction pathway is being explored for early chemoprevention of non-melanoma skin cancer.

摘要翻译： 

非黑色素瘤皮肤癌的发病率正在上升，而包括使用防晒霜在内的初级预防措施已被证明不足以降低这一发病率。因此，需要化学预防策略。紫外线B可通过损伤DNA和关键靶基因的突变，以及促进已启动细胞的克隆扩增，从而引发良性皮肤肿瘤的形成。目前，针对紫外线信号转导通路中的关键分子进行干预，已被探索用于非黑色素瘤皮肤癌的早期化学预防。

原文链接：

Prevention of non-melanoma skin cancer by targeting ultraviolet-B-light signalling