Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer.
Up-regulation of DNA-dependent protein kinase activity and Sp1 in colorectal cancer.
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DOI：
10.3892/ijo.25.2.461
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发表时间：
2004-08
影响因子：
5.2
通讯作者：
Y. Hosoi;Toshiaki Watanabe;K. Nakagawa;Y. Matsumoto;A. Enomoto;A. Morita;H. Nagawa;N. Suzuki
中科院分区：
文献类型：
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作者：
Y. Hosoi;Toshiaki Watanabe;K. Nakagawa;Y. Matsumoto;A. Enomoto;A. Morita;H. Nagawa;N. Suzuki
研究了12例结直肠癌患者肿瘤组织与邻近正常组织在以下方面的定量差异：1)参与DNA双链面包修复的DNA依赖性蛋白激酶（DNA- pk）活性；2)Ku70、Ku80、DNA- pkcs和转录因子Sp1的蛋白和mRNA水平。肿瘤组织中DNA-PK活性及Ku70、Ku80、DNA-PKcs和Sp1蛋白/mRNA水平均显著高于正常组织。DNA-PK活性与Ku70、Ku80、DNA-PKcs和Sp1蛋白/mRNA水平呈显著相关。由于Ku80和DNA- pkcs在其启动子区具有一致的Sp1识别元件，因此对Ku70启动子区DNA序列进行了分析。对Ku70启动子区域的分析表明，Ku70基因在其启动子区域具有一致的Sp1识别元件。Ku70、Ku80和DNA-PKcs mRNA水平呈显著相关，Sp1蛋白水平与Ku70、Ku80 mRNA水平呈显著相关。这些结果表明，结直肠癌患者肿瘤组织中DNA-PK活性以及Ku70、Ku80和DNA-PKcs蛋白和mrna水平升高是由于肿瘤组织中Sp1蛋白水平升高所致。
Tumor tissues and adjacent normal tissues in 12 colorectal cancers were examined for quantitative differences in: i) activity of DNA-dependent protein kinase (DNA-PK), which functions in DNA double-strand breads repair, and ii) protein and mRNA levels of Ku70, Ku80, DNA-PKcs and transcriptional factor Sp1. DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were significantly higher in the tumor tissues compared with the normal tissues. Significant correlations between DNA-PK activity and protein/mRNA levels of Ku70, Ku80, DNA-PKcs and Sp1 were observed. Because Ku80 and DNA-PKcs have consensus Sp1 recognition elements in their promoter region, the DNA sequence of Ku70 promoter region was analyzed. Analysis of Ku70 promoter region reveled that Ku70 gene has consensus Sp1 recognition elements in its promoter region. mRNA levels of Ku70, Ku80 and DNA-PKcs were correlated with one another, and significant correlations between Sp1 protein level and mRNA levels of Ku70 and Ku80 were observed. These results suggest that DNA-PK activity and protein- and mRNA-levels of Ku70, Ku80 and DNA-PKcs were elevated in tumor tissues in patients with colorectal cancer because of elevated Sp1 protein levels in tumor tissues.