用cDNA Array探讨鼻咽癌组织TP53积聚的可能原因

Possible Mechanism of TP53 Accumulation in Nasopharyngeal Carcinoma by Atlas Human Cancer cDNA Expression Array

目的：用cDNA Array 比较鼻咽癌组织及正常组织基因表达谱，寻找鼻咽癌组织TP53积聚的可能原因。方法：（1）Atlas Human Cancer cDNA Expression Array 7742-1滤膜杂交。（2）AtlasImage 1.01a分析滤膜杂交结果。（3）RT-PCR反应验证滤膜杂交结果。（4）免疫组化证实基因在蛋白质水平的表达改变。结果：（1）588个肿瘤相关基因中，共有134个基因表达上调，88个基因表达下调。（2）膜上有TP53调节基因32种。其中13种显示差异表达，有11个表达上调，2个表达下调。（3）TP53上游的蛋白激酶基因ATM和JNK2表达呈上调趋势。（4）泛素降解系统的两个基因ubiquitin-conjugating enzyme E2（M74524）ubiquitin-conjugating enzyme E2 （L22005）mRNA在鼻咽癌和正常鼻咽组织内的表达没有明显改变。结论：（1）在鼻咽癌组织内，TP53的功能失控。（2）ATM和JNK极有可能是TP53积聚的重要原因。

Objective：The aim of this study was to compare gene expression map of nasopharyngeal carcinoma (NPC) tissue with that of control tissue by cDNA Array and to discuss possible reasons of TP53 accumulation in NPC tissue. Methods：(1) hybridization of Atlas Human Cancer cDNA Expression Array 7742-1;(2) analysis of Atlas Arrays using AtlasImage 1.01a;(3) verification of results of array by RT-PCR;(4) verification of proteins expression alteration by immunohistochemistry. Results：(1) Of 588 tumor-related genes, 134 genes were upregulated, 88 downregulated;(2) Of 32 TP53-regulated genes, 13 genes were shown differential expression, 11 upregulated, 2 downregulated;(3) ATM and JNK2 were upregulated;(4) mRNA expression of ubiquitin-conjugating enzyme E2 （M74524）and ubiquitin- conjugating enzyme E2 （L22005）was shown no evident changes. Conclusion：(1) TP53 dysfunction exists in NPC tissues; (2) ATM and JNK might be the important causes of TP53 accumulation.