突变型p53与胃癌多重耐药基因表达的相关性研究

目的研究突变型p53与MDR-1基因间相互关系，探讨p53途径对防治肿瘤细胞多重耐药的意义。方法取胃癌组织切片，采用免疫组化方法检测组织切片p53蛋白和MDR-1基因蛋白产物Pg糖蛋白，分析突变型p53与MDR-1基因表达产物的相互关系。将突变型p53、sv40Tag（封闭p53）导入胃癌细胞株中，观察胃癌细胞株中MDR-1基因mRNA表达的变化。结果46例胃癌组织中p53蛋白阳性率为60．9％，Pg蛋白阳性率为73．9％。在28例p53蛋白阳性表达中有23例（82．1％）Pg蛋白表达阳性。18例p53蛋白阴性表达中9例（50．O％）为Pg蛋白表达阳性。p53和Pg蛋白之间的相关性有显著性意义（P〈0．05）。导入突变型p53细胞组的MDR-1基因mRNA表达比导入突变型p53＋sv40Tag细胞组、对照组MDR-1基因mRNA表达增强。结论突变型p53可能促进肿瘤细胞MDR-1基因表达，使肿瘤细胞更易产生耐药。

Study on relationship between mutant p53 and multidrug resistance gene 1 in gastric cancer

Objective To investigate the relationship between mutant p53 and multidrug resistant gene 1(MDR-1) in gastric cancer.Methods Tissue sections were obtained from 46 cases of gastric cancer.The level of p53 protein and MDR-1 gene product(PgP) were examined using immunohistochemical techniques.Recombinant mutant p53(mp53) and sv40Tag genes were constructed.The recombinant mp53 and mp53+sv40Tag were transferred to gastric cancer cells,the expression of MDR-1 mRNA was detected with RT-PCR.Results Positive p53 was detected in 60.9%(28/46) samples and positive PgP in 73.9%(34/46) samples;and Pgp expression was detected in 23 of 28 p53-positive samples,and 9 of 18 p53-negative samples;p53 expression was positively associated with PgP(P<0.05).Cancer cells transfected with mutant p53 showed higher MDR-1 mRNA than cancer cells transfected with mp53+sv40Tag and control.Conclusion The results demonstrate that mutant p53 may accelerate the MDR-1 gene expression.