p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines.
p53 functional activation is independent of its genotype in five esophageal squamous cell carcinoma cell lines.
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DOI：
10.1007/s11684-010-0260-x
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发表时间：
2010-12-01
期刊：
影响因子：
--
通讯作者：
Zhan, Qimin
中科院分区：
文献类型：
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作者：
Ji, Junfang;Wu, Kun;Zhan, Qimin
p53基因突变存在于食管鳞状细胞癌（esophageal squamous cell carcinoma，ESCC）的临床标本和细胞系中。我们推断，在这些标本和细胞系中可能存在野生型p53的功能失活或突变型p53的功能激活。在这项研究中，我们确定了五种不同的食管鳞癌细胞系中p53功能激活与其基因型之间的相关性。为了检测p53在某些ESCC细胞系中的潜在活化，采用DNA损伤方法包括X射线暴露和顺铂处理来处理细胞。进一步用Western blot和RT-PCR检测DNA损伤后p53蛋白和p53靶基因的表达。结果表明，在p53突变的KYSE 30细胞系和p53野生型的KYSE 150细胞系中，p53可被DNA损伤激活。然而，在具有野生型p53的YES 2、具有突变型p53的KYSE 70和具有未知p53基因型的EC 9706中，p53不能在DNA损伤后被激活。我们的所有数据表明，p53在某些细胞中的功能与其基因型并不密切相关。为了判断p53在特定细胞系中的功能，重要的是检查p53功能激活，而不是简单地依赖于p53基因型。
p53 mutations have been found in many esophageal squamous cell carcinoma (ESCC) clinical specimens and cell lines. We reasoned that functional inactivation of wild-type p53 or the functional activation of mutant-type p53 might exist in these specimens and cell lines. In this study, we identified the correlation between p53 functional activation and its genotype in five different ESCC cell lines. To examine the potential p53 activation in a certain ESCC cell line, DNA damage methods including X-ray exposure and cisplatin treatment were employed to treat cells. Further, the expression of p53 protein and four transcripts of well-known p53 target genes were investigated using Western blot and reverse transcriptionpolymerase chain reaction (RT-PCR) after cell exposure to DNA damage. The results showed that in KYSE 30 cell line with mutant p53 and KYSE 150 with wild-type p53, p53 could be activated by DNA damages. However, p53 could not be activated following the DNA damages in YES 2 with wild-type p53, KYSE 70 with mutant p53, and EC9706 with unknown p53 genotype. All our data indicated that p53 function in certain cells is not closely correlated with its genotype. To judge p53 function in a particular cell line, it is important to examine the p53 functional activation, but not to simply rely on the p53 genotype.