Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells.
Expression of pluripotent stem cell reprogramming factors by prostate tumor initiating cells.
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DOI：
10.1016/j.juro.2009.12.092
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发表时间：
2010-05
期刊：
影响因子：
--
通讯作者：
Siemann DW
中科院分区：
文献类型：
--
作者：
Bae KM;Su Z;Frye C;McClellan S;Allan RW;Andrejewski JT;Kelley V;Jorgensen M;Steindler DA;Vieweg J;Siemann DW
我们在前列腺肿瘤细胞系和原发性前列腺癌组织中发现了一个离散的干细胞样肿瘤细胞群，表达5种必要的转录因子，这些转录因子是重编程多能性所必需的。采用半定量逆转录聚合酶链反应、组织学和免疫组化分析方法，对DU145和PC3人前列腺癌细胞系（ATCC®）、前列腺癌患者肿瘤组织和正常前列腺组织的重编程因子OCT3/4 （cell Signaling Technology®）、SOX2、Klf4 （Santa Cruz Biotechnology, Santa Cruz, California）、Nanog （biolgend®）和c-Myc （cell Signaling）进行检测。利用E-cadherin （R&D Systems®）作为表面标记物，通过流式细胞术细胞分选富集干细胞样肿瘤细胞，并通过软琼脂、球形和致瘤性实验确认肿瘤干细胞样特征。转录因子OCT3/4与SOX2在原发性前列腺肿瘤组织样本中的mRNA表达高度相关。前列腺癌组织中表达OCT3/4或SOX2的细胞数量较正常前列腺组织和良性前列腺增生组织显著增加（p <0.05）。通过流式细胞术从DU145和PC3前列腺癌细胞系中分离得到高表达OCT3/4和SOX2水平的干细胞样肿瘤细胞在免疫缺陷小鼠中表现出高致瘤性。短发夹RNA敲低OCT3/4或SOX2可抑制亲本DU145和PC3前列腺癌细胞的体内生长。研究表明，表达多能干细胞转录因子的前列腺肿瘤细胞具有高度的致瘤性。识别这些细胞及其在前列腺癌生长中的重要性可以为前列腺癌治疗提供新的靶向策略。
We identified a discrete population of stem cell-like tumor cells expressing 5 essential transcription factors required to reprogram pluripotency in prostate tumor cell lines and primary prostate cancer tissue. DU145 and PC3 human prostate cancer cell lines (ATCC®), tumor tissue from patients with prostate cancer and normal prostate tissue were evaluated for the reprogramming factors OCT3/4 (Cell Signaling Technology®), SOX2, Klf4 (Santa Cruz Biotechnology, Santa Cruz, California), Nanog (BioLegend®) and c-Myc (Cell Signaling) by semiquantitative reverse transcriptase-polymerase chain reaction, histological and immunohistochemical analysis. Stem cell-like tumor cells were enriched by flow cytometric cell sorting using E-cadherin (R&D Systems®) as a surface marker, and soft agar, spheroid and tumorigenicity assays to confirm cancer stem cell-like characteristics. mRNA expression of transcription factors OCT3/4 and SOX2 highly correlated in primary prostate tumor tissue samples. The number of OCT3/4 or SOX2 expressing cells was significantly increased in prostate cancer tissue compared to that in normal prostate or benign prostate hyperplasia tissue (p <0.05). When isolated from the DU145 and PC3 prostate cancer cell lines by flow cytometry, stem cell-like tumor cells expressing high OCT3/4 and SOX2 levels showed high tumorigenicity in immunodeficient mice. In vivo growth of the parental DU145 and PC3 prostate cancer cell lines was inhibited by short hairpin RNA knockdown of OCT3/4 or SOX2. Data suggest that prostate tumor cells expressing pluripotent stem cell transcription factors are highly tumorigenic. Identifying such cells and their importance in prostate cancer growth could provide opportunities for novel targeting strategies for prostate cancer therapy.
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影响因子：
8.8
作者：
Hurt, E. M.;Kawasaki, B. T.;Klarmann, G. J.;Thomas, S. B.;Farrar, W. L.
通讯作者：
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影响因子：
30.8
作者：
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通讯作者：
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影响因子：
8.8
作者：
Lang, SH;Sharrard, RM;Maitland, NJ
通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
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影响因子：
11.2
作者：
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通讯作者：
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