• 主题
高级搜索  >
历史搜索 清空历史
首页> 美国卫生研究院文献>British Journal of Cancer >Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer
【2h】

Methylation of tumour suppressor genes APAF-1 and DAPK-1 and in vitro effects of demethylating agents in bladder and kidney cancer

机译：抑癌基因APAF-1和DAPK-1的甲基化以及去甲基化剂在膀胱癌和肾癌中的体外作用

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To examine the significance of the methylation level of the p53 target and tumour suppressor genes apoptotic protease activating factor-1 (APAF-1) and death-associated protein kinase-1 (DAPK-1) in 80 microdissected tumour samples from transitional cell carcinoma (TCC) of the bladder and 80 tumour samples from clear-cell renal cell carcinoma (RCC) as well as from non-tumourous bladder and kidney tissue. Growth-inhibitory effects of the demethylating agents 5-Aza-2′-deoxycytidine (5-Aza-CdR) and zebularine were investigated in TCC and RCC cell lines. The methylation frequency of APAF-1 (DAPK-1) was 100% (77%) in TCC and 100% (33%) in RCC. The methylation levels of APAF-1 could differentiate between the individual tumour stages in TCC as well as in RCC. The APAF-1 methylation levels in RCC were significantly higher in tumours larger than 4 cm and in high-grade tumours. The methylation frequencies in normal tissue for APAF-1 (DAPK-1) were 11% (8%) in bladder tissue and 9% (5%) in kidney tissue. The growth-inhibitory effect of the demethylating agents in TCC (RT4, T24) and RCC (A498, ClearCa-5) cell lines resulted in a 17–132% prolongation of the doubling time (DT). In RCC cell lines, zebularine was superior to 5-Aza-CdR in achieving a DT prolongation. Quantitative real time RT-PCR detected a re-expression of mRNA transcripts of APAF-1 or DAPK-1. In conclusion, demethylating agents effectively retard growth of TCC and RCC cell lines. Methylation level analysis of specific genes has the potential for further tumour characterisation in TCC and RCC.
机译：为了研究p53靶标和肿瘤抑制基因的甲基化水平对凋亡细胞活化因子1（APAF-1）和死亡相关蛋白激酶1（DAPK-1）的甲基化水平的影响，这些标本来自于80例移行细胞癌显微切割的肿瘤样品中（膀胱癌和80个来自透明细胞肾细胞癌（RCC）以及非肿瘤性膀胱和肾脏组织的肿瘤样本。在TCC和RCC细胞系中研究了脱甲基剂5-Aza-2'-脱氧胞苷（5-Aza-CdR）和zebularine的生长抑制作用。在TCC中APAF-1（DAPK-1）的甲基化频率为100％（77％），在RCC中为100％（33％）。 APAF-1的甲基化水平可以区分TCC和RCC中的各个肿瘤阶段。在大于4cm的肿瘤和高级别肿瘤中，RCC中的APAF-1甲基化水平显着更高。正常组织中，APAF-1（DAPK-1）的甲基化频率在膀胱组织中为11％（8％），在肾脏组织中为9％（5％）。去甲基化剂在TCC（RT4，T24）和RCC（A498，ClearCa-5）细胞系中的生长抑制作用导致倍增时间（DT）延长17–132％。在RCC细胞系中，zebularine在实现DT延长方面优于5-Aza-CdR。实时定量RT-PCR检测到APAF-1或DAPK-1的mRNA转录物重新表达。总之，脱甲基剂有效地抑制了TCC和RCC细胞系的生长。特定基因的甲基化水平分析有可能在TCC和RCC中进一步表征肿瘤。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号