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首页> 外文期刊>Molecular and Cellular Biochemistry: An International Journal for Chemical Biology >Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1.
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Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1.

机译：来自人前列腺癌细胞系22RV1的多药耐药性，前列腺癌起始干细胞的建立和表征。

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摘要

Multi-drug resistance is an important element which leads to ineffectiveness of chemotherapeutics. To identify subpopulations of cancerous prostate cells with multi-drug resistance and cancer stem-cell properties has recently become a major research interest. We identified a subpopulation from the prostate cancer cell line 22RV1, which have high surface expression of both CD117 and ABCG2. We found this subpopulation of cells termed CD117(+)/ABCG2(+) also overexpress stem cells markers such as Nanog, Oct4, Sox2, Nestin, and CD133. These cells are highly prolific and are also resistant to treatment with a variety of chemotherapeutics such as casplatin, paclitaxel, adriamycin, and methotrexate. In addition, CD117(+)/ABCG2(+) cells can readily establish tumors in vivo in a relatively short time. To investigate the mechanism of aggressive tumor growth and drug resistance, we examined the CpG islands on the ABCG2 promoter of CD117(+)/ABCG2(+) cells and found they were remarkably hypomethylated. Furthermore, chromatin immunoprecipitation assays revealed high levels of both histone 3 acetylation and H3K4 trimethylation at the CpG islands on the ABCG2 promoter. Our these data suggest that CD117(+)/ABCG2(+) cells could be reliably sorted from the human prostate cancer cell line 22RV1, and represent a valuable model for studying cancer cell physiology and multi-drug resistance. Furthermore, identification and study of these cells could have a profound impact on selection of individual treatment strategies, clinical outcome, and the design or selection of the next generation of chemotherapeutic agents.
机译：多药耐药性是导致化学治疗无效的重要因素。鉴定具有多药耐药性和癌症干细胞特性的癌性前列腺细胞亚群近来已成为主要研究兴趣。我们从前列腺癌细胞系22RV1中鉴定出一个亚群，该细胞系同时具有CD117和ABCG2的高表面表达。我们发现这种称为CD117（+）/ ABCG2（+）的细胞亚群也过表达干细胞标记，例如Nanog，Oct4，Sox2，Nestin和CD133。这些细胞是高产的，并且还对多种化学疗法（例如卡铂，紫杉醇，阿霉素和甲氨蝶呤）的治疗具有抗性。此外，CD117（+）/ ABCG2（+）细胞可以在相对较短的时间内在体内轻松建立肿瘤。若要研究侵略性肿瘤生长和耐药性的机制，我们检查了CD117（+）/ ABCG2（+）细胞ABCG2启动子上的CpG岛，发现它们明显地被低甲基化。此外，染色质免疫沉淀测定法揭示了ABCG2启动子上CpG岛的组蛋白3乙酰化和H3K4三甲基化水平很高。我们的这些数据表明，CD117（+）/ ABCG2（+）细胞可以可靠地从人前列腺癌细胞系22RV1中分选出来，并代表了研究癌细胞生理学和多药耐药性的有价值的模型。此外，这些细胞的鉴定和研究可能对个体治疗策略的选择，临床结果以及下一代化疗药物的设计或选择产生深远的影响。

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