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p53 信号通路在皮肤基底细胞癌中的作用:免疫组化描述。

The p53 Signalling Pathway in Cutaneous Basal Cell Carcinoma: An Immunohistochemical Description.

出版信息

Acta Derm Venereol. 2020 Mar 31;100(6):adv00098. doi: 10.2340/00015555-3420.

Abstract

Basal cell carcinoma (BCC) is the most common malignant tumour of the skin. The incidence of BCC is increasing, and the disease represents a major medical and economic problem. UV radiation and other genotoxic agents have been shown to cause different types of both direct and indirect DNA damage (1), including the generation of pyrimidine dimers and DNA double-strand breaks (DSBs). In addition to mutations in the sonic hedgehog pathway, which represent the molecular hallmark of BCC pathogenesis, mutations in the p53 gene are frequently detected in these malignancies. However, the relevance of this finding is not completely understood; thus, the aim of this investigation was to elucidate the relevance of the p53 pathway in the pathogenesis of BCC by immunohistochemically analysing the expression of some major proteins involved in p53-mediated cellular signalling, namely p53, ΔNp63, TAp73, and MDM2. Because p53 is activated by DNA damage to either arrest the cell cycle or induce apoptosis, we also immunohistochemically analysed the expression of γ-H2AX, an early sensor of DNA damage.

摘要

基底细胞癌 (BCC) 是最常见的皮肤恶性肿瘤。BCC 的发病率正在上升,这种疾病是一个主要的医学和经济问题。紫外线辐射和其他遗传毒性剂已被证明会导致不同类型的直接和间接 DNA 损伤 (1),包括嘧啶二聚体和 DNA 双链断裂 (DSBs) 的产生。除了 sonic hedgehog 通路中的突变,这些突变是 BCC 发病机制的分子标志外,p53 基因的突变也经常在这些恶性肿瘤中被检测到。然而,这一发现的相关性尚不完全清楚;因此,本研究旨在通过免疫组织化学分析参与 p53 介导的细胞信号通路的一些主要蛋白的表达,即 p53、ΔNp63、TAp73 和 MDM2,阐明 p53 通路在 BCC 发病机制中的相关性。由于 p53 被 DNA 损伤激活,以阻止细胞周期或诱导细胞凋亡,我们还通过免疫组织化学分析 γ-H2AX 的表达情况,γ-H2AX 是 DNA 损伤的早期传感器。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6837/9128888/114543454f4c/ActaDV-100-6-5681-g001.jpg

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