Erb Peter, Ji Jingmin, Wernli Marion, Kump Erwin, Glaser Andrea, Büchner Stanislaw A
Institute for Medical Microbiology, University of Basel, Petersplatz 10, CH-4003 Basel, Switzerland.
Immunol Lett. 2005 Aug 15;100(1):68-72. doi: 10.1016/j.imlet.2005.06.008.
Long-term ultraviolet-light (UV) exposure of human skin epidermis is associated with an increased risk for the development of skin cancers, such as melanoma, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). UV radiation not only induces DNA damage in epidermal cells, it also interferes with skin homeostasis, which is maintained by a unique distribution pattern of apoptosis-inducing and -preventing molecules. If the DNA damage is not repaired or the damaged cells are not eliminated by apoptosis, the consequence can be cell transformation, uncontrolled proliferation and eventually skin tumor formation. An important "repair" gene is the p53 suppressor gene. Excessive UV exposure can mutate the p53 gene leading to the loss of its repair function and thus apoptosis resistance of the DNA-damaged cell. For BCC formation an additional pathway has been identified. Mutation of genes of the Hedgehog signaling pathway evokes the downregulation of apoptotic genes and upregulation of anti-apoptotic genes preventing the elimination of damaged cells. In addition, BCC and SCC strongly express the apoptosis-inducing Fas-ligand (FasL) which may help the tumor to escape the attack of immune effector cells. Silencing the genes involved in tumor formation by RNA interference might become a promising new approach to treat skin tumors.
长期将人类皮肤表皮暴露于紫外线下会增加患皮肤癌的风险，如黑素瘤、基底细胞癌（BCC）和鳞状细胞癌（SCC）。紫外线辐射不仅会诱导表皮细胞中的DNA损伤，还会干扰皮肤的稳态，而这种稳态是由诱导凋亡和防止凋亡分子的独特分布模式维持的。如果DNA损伤未得到修复或受损细胞未通过凋亡被清除，结果可能是细胞转化、不受控制的增殖并最终形成皮肤肿瘤。一个重要的“修复”基因是p53抑癌基因。过度暴露于紫外线会使p53基因发生突变，导致其修复功能丧失，从而使DNA受损细胞具有抗凋亡能力。对于基底细胞癌的形成，还发现了另一条途径。刺猬信号通路基因的突变会导致凋亡基因下调和抗凋亡基因上调，从而阻止受损细胞的清除。此外，基底细胞癌和鳞状细胞癌强烈表达诱导凋亡的Fas配体（FasL），这可能有助于肿瘤逃避免疫效应细胞的攻击。通过RNA干扰使参与肿瘤形成的基因沉默可能成为一种有前景的治疗皮肤肿瘤的新方法。
