Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells.
Deficient Nucleotide Excision Repair in Squamous Cell Carcinoma Cells.
复制标题
鳞状细胞癌细胞中缺乏的核苷酸切除修复。
DOI：
10.1111/php.12625
复制
发表时间：
2016
影响因子：
3.3
通讯作者：
Oh,DennisH
中科院分区：
文献类型：
--
作者：
Dong,TiffanyK;Ona,Katherine;Scandurra,AmyE;Demetriou,StephanieK;Oh,DennisH
鳞状细胞癌（SCC）与紫外线辐射和多种遗传变化有关，但导致遗传不稳定的机制尚不清楚。比较SCC细胞系与正常角质形成细胞对紫外线辐射的敏感性、DNA修复动力学和DNA修复蛋白表达。相对于正常角质形成细胞，四种SCC细胞系均对紫外线辐射不敏感，并且除了SCC 25细胞系之外，缺乏环丁烷嘧啶二聚体的整体修复，尽管不是6 - 4光产物。环丁烷嘧啶二聚体损伤的DNA修复与XC基因mRNA表达减少有关，但与DDB 2基因无关，DDB 2基因编码关键的DNA损伤识别蛋白。然而，XPC或DDB 2蛋白或两者的水平在修复缺陷型SCC细胞系中显著降低。p53水平与DNA修复活性或XPC和DDB 2水平无关，但p63水平在整体修复减少的细胞系中缺乏。缺乏p63的修复熟练SCC 25细胞失去了XPC表达，早期整体DNA修复活性和UV抗性。这些结果表明，一些SCC细胞系缺乏整体核苷酸切除修复，并支持p63作为SCC中核苷酸切除修复的调节剂的作用。
Squamous cell carcinomas (SCCs) are associated with ultraviolet radiation and multiple genetic changes, but the mechanisms leading to genetic instability are unclear. SCC cell lines were compared to normal keratinocytes for sensitivity to ultraviolet radiation, DNA repair kinetics and DNA repair protein expression. Relative to normal keratinocytes, four SCC cell lines were all variably sensitive to ultraviolet radiation and, except for the SCC25 cell line, were deficient in global repair of cyclobutane pyrimidine dimers, although not 6‐4 photoproducts. Impaired DNA repair of cyclobutane pyrimidine dimers was associated with reduced mRNA expression fromXPCbut notDDB2genes which each encode key DNA damage recognition proteins. However, levels of XPC or DDB2 proteins or both were variably reduced in repair‐deficient SCC cell lines. p53 levels did not correlate with DNA repair activity or with XPC and DDB2 levels, but p63 levels were deficient in cell lines with reduced global repair. Repair‐proficient SCC25 cells depleted of p63 lost XPC expression, early global DNA repair activity and UV resistance. These results demonstrate that some SCC cell lines are deficient in global nucleotide excision repair and support a role for p63 as a regulator of nucleotide excision repair in SCCs.