Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells.
Sequential coexpression of the multidrug resistance genes MRP and mdr1 and their products in VP-16 (etoposide)-selected H69 small cell lung cancer cells.
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发表时间：
1995-02
期刊：
影响因子：
11.2
通讯作者：
Inger Brock;D. Hipfner;B. S. Nielsen;P. B. Jensen;R. Deeley;S. Cole;M. Sehested
中科院分区：
文献类型：
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作者：
Inger Brock;D. Hipfner;B. S. Nielsen;P. B. Jensen;R. Deeley;S. Cole;M. Sehested
多药耐药表型中的耐药归因于mdr 1或MRP基因及其产物在许多细胞系中的过表达，而据我们所知，在相同细胞中的共表达以前尚未报道。人小细胞肺癌H69/VP细胞通过在增加剂量的VP-16中连续孵育而形成。在逆转录-PCR检测中，我们发现H69/VP细胞中mdr 1和多药耐药蛋白（MRP）基因的过度表达，免疫印迹显示P-糖蛋白和MRP均升高。双重免疫细胞化学染色显示MRP和P-糖蛋白在相同的细胞中表达，表明观察结果不是来自两个独立克隆的选择。对H69/VP细胞早期传代的检测显示MRP mRNA的过表达发生在mdr 1之前。因此，未来的细胞系和临床样本应同时进行mdr 1/P-糖蛋白和MRP检测，因为其中一种表型的阳性结果并不排除另一种表型的存在。
Resistance to drugs included in the multidrug-resistance phenotype has been attributed to overexpression of either mdr1 or MRP genes and their products in numerous cell lines, while coexpression, to our knowledge, has not previously been reported in the same cells. Human small cell lung cancer H69/VP cells were developed by continuous incubation in increasing doses of VP-16. In reverse transcription-PCR assays we found over-expression of both mdr1 and multidrug-resistance protein (MRP) genes, and immunoblots showed both elevated P-glycoprotein and MRP in H69/VP cells. Double immunocytochemical staining demonstrated the expression of both MRP and P-glycoprotein in the same cells, indicating that the observations do not result from the selection of two independent clones. Examination of early passages of H69/VP cells showed that overexpression of MRP mRNA occurred prior to mdr1. Thus, cell lines and clinical samples in the future should be tested for both mdr1/P-glycoprotein and MRP since a positive result for one of the phenotypes does not preclude the existence of the other.