Galimberti S, Marchetti A, Buttitta F, Carnicelli V, Pellegrini S, Bevilacqua G, Petrini M
Oncology Department, University of Pisa, Italy.
Anticancer Res. 1998 Jul-Aug;18(4C):2973-6.
Many genes (mdr1, mrp, DNA topoisomerases II) are known to be involved in the resistance to unrelated drugs (the MDR phenomenon), but the mechanisms of their activation have to be further investigated.
Because several authors showed that p53 mutated gene was able to induce mdr1 overexpression, we evaluated in 51 non small cell lung cancer samples, already tested for p53 mutations, the expression of mdr1, mrp, DNA topoisomerase II alpha and beta mRNAs by qualitative RT-PCR assays.
Mutations of p53 were found in 56% of cases. Mdr1 expression was detected in 27%, mrp in 100%, topoisomerase alpha in 82% and beta in 94% of the samples.
It was not possible to detect any relationship between the expression of the MDR-related genes and tumor histological type, stage or lymph node involvement. Nevertheless, a close association between p53 alterations and either mdr1 gene (p = 0.001) or DNA topoisomerase II alpha (p = 0.003) expression was found.
已知许多基因(多药耐药基因1、多药耐药相关蛋白、DNA拓扑异构酶II)与对不相关药物的耐药性有关(多药耐药现象),但其激活机制仍需进一步研究。
由于几位作者表明p53突变基因能够诱导多药耐药基因1的过表达,我们对51例已检测p53突变的非小细胞肺癌样本,通过定性逆转录聚合酶链反应检测多药耐药基因1、多药耐药相关蛋白、DNA拓扑异构酶IIα和βmRNA的表达。
56%的病例发现p53突变。27%的样本检测到多药耐药基因1表达,100%检测到多药耐药相关蛋白表达,82%检测到拓扑异构酶α表达,94%检测到拓扑异构酶β表达。
无法检测到多药耐药相关基因表达与肿瘤组织学类型、分期或淋巴结受累之间的任何关系。然而,发现p53改变与多药耐药基因1(p = 0.001)或DNA拓扑异构酶IIα(p = 0.003)表达之间存在密切关联。