Nucleotide Excision Repair Gene Expression after Cisplatin Treatment in Melanoma
Nucleotide Excision Repair Gene Expression after Cisplatin Treatment in Melanoma
复制标题
DOI：
10.1158/0008-5472.can-10-0161
复制
发表时间：
2010-10-15
期刊：
影响因子：
11.2
通讯作者：
Scott, Rodney J.
中科院分区：
文献类型：
--
作者：
Bowden, Nikola A.;Ashton, Katie A.;Scott, Rodney J.
黑色素瘤的两个标志性特征是由于慢性紫外线辐射暴露和顺铂在疾病治疗中的有限功效而发展。这两种DNA损伤剂都导致大的螺旋扭曲DNA损伤，其通过核苷酸切除修复（NER）被识别和修复。本研究的目的是检查NER基因转录，p53和p21的表达与顺铂治疗的黑色素瘤细胞系相比，黑素细胞。与黑素细胞相比，所有基因的基础表达在黑色素瘤细胞系中更高。顺铂治疗后24小时，黑色素瘤细胞系中的全基因组修复（GGR）转录物的相对表达（RE）显著降低。与黑素细胞相比，黑色素瘤细胞系中p53的基础RE显著更高。然而，仅在顺铂处理后6小时和24小时在黑素细胞中诱导p53。在顺铂处理后6和24小时，抑制p53表达显著降低黑素细胞中所有GGR转录物的表达。虽然RE水平随着p53抑制而降低，但GGR基因的诱导与对照黑素细胞中的非常相似，并且在各个时间点显著增加。这项研究的结果显示，顺铂治疗后24小时，黑色素瘤细胞中GGR转录水平降低。我们的研究结果表明，顺铂治疗的有限疗效和紫外线在黑色素瘤中的可能作用的可能机制的解释。Cancer Res; 70（20）; 7918-26. (C)2010年AACR。
Two of the hallmark features of melanoma are its development as a result of chronic UV radiation exposure and the limited efficacy of cisplatin in the disease treatment. Both of these DNA-damaging agents result in large helix-distorting DNA damage that is recognized and repaired by nucleotide excision repair (NER). The aim of this study was to examine the expression of NER gene transcripts, p53, and p21 in melanoma cell lines treated with cisplatin compared with melanocytes. Basal expression of all genes was greater in the melanoma cell lines compared with melanocytes. Global genome repair (GGR) transcripts showed significantly decreased relative expression (RE) in melanoma cell lines 24 hours after cisplatin treatment. The basal RE of p53 was significantly higher in the melanoma cell lines compared with the melanocytes. However, induction of p53 was only significant in the melanocytes at 6 and 24 hours after cisplatin treatment. Inhibition of p53 expression significantly decreased the expression of all the GGR transcripts in melanocytes at 6 and 24 hours after cisplatin treatment. Although the RE levels were lower with p53 inhibition, the induction of the GGR genes was very similar to that in the control melanocytes and increased significantly across the time points. The findings from this study revealed reduced GGR transcript levels in melanoma cells 24 hours after cisplatin treatment. Our findings suggest a possible mechanistic explanation for the limited efficacy of cisplatin treatment and the possible role of UV light in melanoma. Cancer Res; 70(20); 7918-26. (C) 2010 AACR.