Characterization of canine MDR1 mRNA: its abundance in drug resistant cell lines and in vivo.

Characterization of canine MDR1 mRNA: its abundance in drug resistant cell lines and in vivo.
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DOI:
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发表时间:
1998
影响因子:
2
通讯作者:
S. Steingold;N. Sharp;M. Mcgahan;C. S. Hughes;S. Dunn;R. Page
S. Steingold;N. Sharp;M. Mcgahan;C. S. Hughes;S. Dunn;R. Page
中科院分区:
医学4区
文献类型:
--
作者:
S. Steingold;N. Sharp;M. Mcgahan;C. S. Hughes;S. Dunn;R. Page

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背景MDR 1基因的过表达常常导致耐药。本研究的目的是表征犬MDR 1 mRNA同源物,并评估其在犬细胞系和淋巴瘤中的表达。材料与方法采用半定量RT/PCR技术,在三种耐药细胞系和治疗前犬淋巴瘤中评估犬MDR 1转录物的丰度。结果犬MDR 1基因转录产物大小为4.5Kb,与人MDR 1基因的同源性为93%,与小鼠和仓鼠的同源性为90%。在三种渐进性耐药犬细胞系中观察到MDR 1转录水平增加。在患有淋巴瘤的狗中,从头MDR 1转录物表达与对治疗的反应无关。结论:我们得出结论,犬MDR 1 mRNA同源物在结构上类似于人的转录本。在犬淋巴瘤中,MDR 1 mRNA的表达与体外药物敏感性相关,但与体内阿霉素敏感性无关。
BACKGROUND Overexpression of the MDR1 gene often contributes to antineoplastic drug resistance. The purpose of this study was to characterize the canine MDR1 mRNA homologue and evaluate its expression in both canine cell lines and lymphomas. MATERIALS AND METHODS The abundance of the canine MDR1 transcript was assessed in three resistant cell lines and in pretreatment canine lymphoma using semi-quantitative RT/PCR. RESULTS Canine transcript was 4.5 Kb with 93% sequence homology to human MDR1, and 90% homology to mouse and hamster equivalent genes. Increase in MDR1 transcript levels was observed in three progressively resistant canine cell lines. De novo MDR1 transcript expression was independent of response to therapy in dogs with lymphoma. CONCLUSIONS We conclude that the canine MDR1 mRNA homologue is structurally similar to the human transcript. Expression of MDR1 mRNA correlates with in vitro drug sensitivity but does not correlate with in vivo doxorubicin sensitivity in canine lymphoma.