Roles of the transcription factor p53 in keratinocyte carcinomas
Roles of the transcription factor p53 in keratinocyte carcinomas
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DOI：
10.1111/j.1365-2133.2006.07230.x
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发表时间：
2006-05-01
影响因子：
10.3
通讯作者：
Brash, DE
中科院分区：
文献类型：
--
作者：
Brash, DE
转录因子 p53 在大多数角质形成细胞癌（非黑色素瘤皮肤癌）中发生突变。在这些肿瘤中，基因带有其诱变剂——阳光的痕迹。阳光诱导的 p53 突变也见于皮肤癌前病变，甚至是暴露在阳光下的皮肤，其中含有数千个 p53 突变角质形成细胞克隆。正常的 p53 会因阳光照射而上调，之后它以多种方式发挥肿瘤抑制因子的作用：增加 DNA 修复、阻止细胞周期并诱导严重受损的角质形成细胞凋亡。这种紫外线诱导的上调已被用作评估防晒霜有效性的分析方法。然而，一旦突变，p53 就会使细胞具有抗凋亡能力，因此对阳光过度照射的敏感度低于正常细胞。这种角色的逆转驱动癌前角质形成细胞的克隆扩张。
The transcription factor p53 is mutated in most keratinocyte carcinomas (nonmelanoma skin cancers). In these tumours, the gene bears the trace of its mutagen, sunlight. Sunlight-induced p53 mutations are also seen in skin precancers and even sun-exposed skin, which harbours thousands of p53-mutant keratinocyte clones. Normal p53 is upregulated by sunlight exposure, after which it acts as a tumour suppressor in several ways: increasing DNA repair, arresting the cell cycle and inducing apoptosis of badly damaged keratinocytes. This UV-induced upregulation has been used as an assay for assessing the effectiveness of sunscreens. Once mutated, however, p53 renders cells apoptosis-resistant and therefore less sensitive to sunlight overexposure than normal cells. This reversal of roles drives clonal expansion of precancerous keratinocytes.