Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86.
Radioresistant cervical cancer shows upregulation of the NHEJ proteins DNA-PKcs, Ku70 and Ku86.
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DOI：
10.1038/sj.bjc.6605201
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发表时间：
2009-09-01
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
宫颈癌的早期症状有哪些？DNA双链断裂的形成被认为是辐射效应的关键。非同源末端连接（NHEJ）蛋白DNA-PKcs、Ku 70和Ku 86在修复DNA损伤中具有主要作用。本研究的目的是分析放射治疗后残留宫颈肿瘤中DNA-PKcs、Ku 70和Ku 86及其下游信号分子p53、p21和Mdm-2的表达是否改变。回顾性分析127例术前放疗和根治性手术治疗的IB-IIA期宫颈癌患者，发现30例患者的宫颈标本中有残留肿瘤。对22例原发灶和残留灶的肿瘤组织进行免疫组化染色，检测DNA-PKcs、Ku 86、Ku 70、p53、p21和Mdm-2的表达。残余肿瘤中DNA-PKcs（P=0.037）、Ku 70（P=0.018）、Ku 86（P=0.008）阳性细胞率增高。原发性和残留肿瘤之间的DNA-PKcs表达的相关性被发现。p21阳性细胞的频率下降（P=0.007），而在残留肿瘤中没有变化，p53或Mdm-2阳性细胞观察。我们的研究结果表明，宫颈癌放疗后有增加的DNA-PK表达。需要对更大的患者队列进行研究，以解释DNA-PK功能的上调可能是这种肿瘤类型中放射抗性机制的一部分。
Radiotherapy is central in the treatment of cervical cancer. The formation of DNA double-strand breaks is considered to be critical for the radiotherapeutic effect. The non-homologous end joining (NHEJ) proteins DNA–PKcs, Ku70 and Ku86 have a major role in repairing DNA lesions. The objective of this study was to analyse if the expression of DNA–PKcs, Ku70 and Ku86 and their downstream signalling molecules p53, p21 and Mdm-2 are altered in residual cervical tumours after radiotherapy. Retrospective analysis of 127 patients with cervical cancer stage IB-IIA treated with preoperative radiotherapy and radical surgery, revealed residual tumour in the cervical specimen in 30 patients. In 22 cases tumour material from residual and corresponding primary tumour were retrieved and the expression of DNA–PKcs, Ku86, Ku70, p53, p21 and Mdm-2 were assessed by immunohistochemistry. Residual tumours showed increased frequency of DNA–PKcs (P=0.037), Ku70 (P=0.018), Ku86 (P=0.008) positive cells. A correlation in DNA–PKcs expression between primary and residual tumours was found. The frequency of p21-positive cells was decreased (P=0.007) in residual tumours whereas no change in p53 or Mdm-2-positive cells were observed. Our results show that cervical carcinoma surviving radiotherapy have an increased DNA–PK expression. Studies on larger patient cohorts are needed to allow an interpretation that an upregulation of DNA–PK function may be part of a radioresistance mechanism within this tumour type.
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DOI：
10.1046/j.1525-1438.2002.01089.x
发表时间：
2002-03-01
影响因子：
4.8
作者：
Beskow, C;Ågren-Cronqvist, AK;Lewensohn, R
通讯作者：
Lewensohn, R
影响因子：
5.7
作者：
Dittmann, K;Mayer, C;Rodemann, HP
通讯作者：
Rodemann, HP
影响因子：
5.3
作者：
LEESMILLER, SP;SAKAGUCHI, K;ANDERSON, CW
通讯作者：
ANDERSON, CW
Ku70的表达与子宫颈癌的存活相关。
影响因子：
8.8
作者：
Wilson, CR;Davidson, SE;Margison, GP;Jackson, SP;Hendry, JH;West, CML
通讯作者：
West, CML
影响因子：
4.8
作者：
Dittmann, K;Mayer, C;Rodemann, HP
通讯作者：
Rodemann, HP