Distribution of multidrug resistance-associated P-glycoprotein in normal and neoplastic human tissue

Distribution of multidrug resistance-associated P-glycoprotein in normal and neoplastic human tissue
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多药耐药相关P-糖蛋白在正常和肿瘤人体组织中的分布

DOI:
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发表时间:
1990
期刊:
影响因子:
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通讯作者:
R. Scheper
R. Scheper
中科院分区:
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文献类型:
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作者:
P. Valk;C. K. Kalken;H. Ketelaars;H. Broxterman;G. Scheffer;C. Kuiper;T. Tsuruo;J. Lankelma;C. Meijer;H. Pinedo;R. Scheper

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摘要P-糖蛋白是一种与某些细胞抑制药物产生多药耐药密切相关的分子,包括阿霉素、长春新碱和柔红霉素。我们用3种针对P-糖蛋白分子不同表位的单抗(JSB-1、MRK16、C219),用常规的免疫过氧化物酶技术,研究了P-糖蛋白在人体正常组织和恶性肿瘤组织中的分布。P-糖蛋白存在于胃肠道上皮、支气管上皮、乳腺、胰管、肾小管、前列腺癌、唾液腺、皮肤汗腺,以及胆小管、肾上腺和各器官毛细血管内皮细胞,尤其是脑。3种抗体的反应模式基本相似,但也有明显不同的染色反应。在各种人类肿瘤中发现了反应性,这些肿瘤起源于正常表达P-糖蛋白的组织。了解这种分子在正常和恶性组织中的分布和功能可能会预测耐药性,从而可能影响治疗的选择。讨论了P-糖蛋白在正常组织中的作用及其对化疗的意义。
Summary P-glycoprotein is a molecule strongly associated with multi-drug resistance to certain cytostatic drugs, including adriamycin, vincristine, and daunorubicin. Using 3 monoclonal antibodies directed at different epitopes of this molecule (JSB-1, MRK16, C219) we investigated the tissue distribution of P-glycoprotein in normal and malignant human tissues, employing a routine immunoperoxidase technique. P-glycoprotein was found in the gastrointestinal epithelium, epithelia of the bronchi, mammary gland, pancreatic ducts, renal tubules, prostate gland, salivary gland, sweat glands of the skin, as well as in bile canaliculi and ductules, the adrenal and in endothelium of capillaries in various organs, most notably the brain. Mostly the pattern of reactivity of the 3 antibodies was similar, but some distinctly different staining reactions were seen. Reactivity was found in a variety of human tumors, arising from tissues normally expressing P-glycoprotein. Knowledge of the distribution and function of this molecule in both normal and malignant tissues may predict resistance and thus may influence choice of therapy. The role of P-glycoprotein in normal tissues and its implications for chemotherapy is discussed.
DOI: 10.1073/pnas.86.2.695
发表时间: 1989-01-01
影响因子: 11.1
作者:
CORDONCARDO, C;OBRIEN, JP;BERTINO, JR
通讯作者: BERTINO, JR