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多药耐药基因(MDR-1)在人正常白细胞中的表达。

Expression of multidrug resistance gene (MDR-1) in human normal leukocytes.

作者信息

Damiani D, Michieli M, Michelutti A, Geromin A, Raspadori D, Fanin R, Savignano C, Giacca M, Pileri S, Mallardi F

机构信息

Cattedra di Ematologia, Policlinico Universitario, Udine, Italy.

出版信息

Haematologica. 1993 Jan-Feb;78(1):12-7.

PMID:8098310
Abstract

BACKGROUND

The mdr-1 gene, which codes for a 170-kd transmembrane glycoprotein (P170), is frequently overexpressed in multidrug resistant (MDR) tumor cell lines and in spontaneous tumors, including leukemia and lymphoma. However, it is also constitutively expressed as a normal gene in normal tissues.

METHODS

We used human mdr-1 cDNA and three anti-P170 monoclonal antibodies (MoAbs: MRK-16, C-219 and JSB-1) to investigate the normal peripheral blood leukocyte content of mdr-1 specific mRNA and of P170 through immunocytochemistry and flow cytometry.

RESULTS

We did not find any increase in mdr-1-specific mRNA, while small amounts of P170 were easily detectable in about two thirds of the lymphocytes and monocytes and in about one third of the granulocytes. The level of P170 expression in leukocytes was similar to that found in non-MDR tumor cell lines.

CONCLUSIONS

mdr-1 is constitutively expressed in human normal leukocytes at levels that cannot significantly affect drug resistance. Accordingly, low-level mdr-1 expression in leukemic cells should not be considered a label of pleiotropic drug resistance.

摘要

背景

多药耐药基因(mdr-1)编码一种170-kd跨膜糖蛋白(P170),在多药耐药(MDR)肿瘤细胞系以及包括白血病和淋巴瘤在内的自发肿瘤中经常过度表达。然而,它在正常组织中也作为一种正常基因组成性表达。

方法

我们使用人mdr-1 cDNA和三种抗P170单克隆抗体(MoAbs:MRK-16、C-219和JSB-1),通过免疫细胞化学和流式细胞术研究mdr-1特异性mRNA和P170在正常外周血白细胞中的含量。

结果

我们未发现mdr-1特异性mRNA有任何增加,而在约三分之二的淋巴细胞和单核细胞以及约三分之一的粒细胞中很容易检测到少量P170。白细胞中P170的表达水平与在非MDR肿瘤细胞系中发现的水平相似。

结论

mdr-1在人正常白细胞中组成性表达,其水平不会显著影响耐药性。因此,白血病细胞中低水平的mdr-1表达不应被视为多药耐药的标志。

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Haematologica. 1993 Jan-Feb;78(1):12-7.
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