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- Title
Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1.
- Authors
Te Liu; Fuhui Xu; Xiling Du; Dongmei Lai; Tianjin Liu; Yarui Zhao; Qin Huang; Lizhen Jiang; Wenbin Huang; Weiwei Cheng; Zhixue Liu
- Abstract
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.
- Subjects
MULTIDRUG resistance; DRUG therapy; CANCER cells; PROSTATE cancer; STEM cells; CELL physiology
- Publication
Molecular & Cellular Biochemistry, 2010, Vol 340, Issue 1/2, p265
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-010-0426-5