Establishment and characterization of multi-drug resistant, prostate carcinoma-initiating stem-like cells from human prostate cancer cell lines 22RV1.
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.
School of Life Science and Technology, Tongji University, 200092 Shanghai, China.
Te
T
Liu
Fuhui
F
Xu
Xiling
X
Du
Dongmei
D
Lai
Tianjin
T
Liu
Yarui
Y
Zhao
Qin
Q
Huang
Lizhen
L
Jiang
Wenbin
W
Huang
Weiwei
W
Cheng
Zhixue
Z
Liu
D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000107:Acetylation; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018899:CpG Islands; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic; D006657:Histones; D006801:Humans; D008297:Male; D008745:Methylation; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011401:Promoter Regions, Genetic; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011499:Protein Processing, Post-Translational; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013997:Time Factors; D047368:Tumor Burden
C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D004791:Enzyme Inhibitors; D006657:Histones; D009363:Neoplasm Proteins; D000077209:Decitabine; D015254:DNA Modification Methylases; D019009:Proto-Oncogene Proteins c-kit; D001374:Azacitidine