McNutt N S, Saenz-Santamaría C, Volkenandt M, Shea C R, Albino A P
Department of Pathology, New York Hospital-Cornell University Medical Center, NY.
Arch Dermatol. 1994 Feb;130(2):225-32.
Abnormalities in the p53 gene and in expression of its protein product are among the most frequent changes demonstrated in a variety of human cancers. p53 Is a nuclear phosphoprotein that in the natural form or "wild-type" can bind to DNA and prevent cells from entering into the S phase of the cell cycle. There is an increase in wild-type p53 after exposure of the skin to UV light, which allows for DNA repair before replication that would make DNA damage permanent. A loss of this protective influence destabilizes the genome. Mutation of the p53 gene commonly causes a defective protein that is degraded more slowly and accumulates in the cell to the extent that it becomes detectable by routine immunocytochemistry. These abnormalities precede the development of cancer in some examples. Studies of precursor lesions have used mainly immunohistochemical techniques that show p53 protein overexpression. The relationship between such overexpression and actual mutation of the p53 gene is controversial because overexpression of "wild-type" p53 protein also can occur. Mutations in the p53 gene have been observed in many actinic keratoses, basal cell carcinomas, and squamous cell carcinomas, and in a small proportion of malignant melanomas. Specific types of pyrimidine transitions have pointed to a role for UV light in these mutations. Molecular analysis is needed to determine whether or not immunocytochemical staining is truly reflective of mutation or is due to some other mechanism that causes an increased expression of wild-type p53.
p53基因及其蛋白质产物表达的异常是多种人类癌症中最常见的变化之一。p53是一种核磷蛋白，其天然形式或“野生型”能够与DNA结合，阻止细胞进入细胞周期的S期。皮肤暴露于紫外线后，野生型p53会增加，这使得在复制（否则会使DNA损伤永久化）之前进行DNA修复。这种保护作用的丧失会使基因组不稳定。p53基因的突变通常会导致一种有缺陷的蛋白质，其降解速度更慢，并在细胞中积累，以至于通过常规免疫细胞化学可以检测到。在某些情况下，这些异常先于癌症的发生。对癌前病变的研究主要使用免疫组织化学技术，显示p53蛋白过表达。这种过表达与p53基因实际突变之间的关系存在争议，因为“野生型”p53蛋白也可能发生过表达。在许多光化性角化病、基底细胞癌和鳞状细胞癌以及一小部分恶性黑色素瘤中都观察到了p53基因的突变。特定类型的嘧啶转换表明紫外线在这些突变中起作用。需要进行分子分析，以确定免疫细胞化学染色是否真的反映了突变，还是由于导致野生型p53表达增加的其他机制。
