期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 340, 期 1-2, 页码 265-273出版社
SPRINGER
DOI: 10.1007/s11010-010-0426-5
关键词
Carcinoma-initiating stem-like cells; ABCG2; Multidrugs resistant; Epigenetic modification; Cell models
类别
资金
- Shanghai Municipal Health Bureau Fund for Young Scholars [2008Y002]
- Medicine-Engineering Unite Fund for Shanghai Jiaotong University [YG2009MS47]
- Shanghai Committee Medical Science Foundation of China [10411967100]
- National High Technology Research and Development Program of China [2008AA101001]
- Science and Technology Department of Shanghai Research Fund [07DZ19063-2]
Multi-drug resistance is an important element which leads to ineffectiveness of chemotherapeutics. To identify subpopulations of cancerous prostate cells with mutli-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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据