Establishment and characterization of a highly tumorigenic African American prostate cancer cell line, E006AA-hT.
Establishment and characterization of a highly tumorigenic African American prostate cancer cell line, E006AA-hT.
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DOI：
10.7150/ijbs.9406
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发表时间：
2014
影响因子：
9.2
通讯作者：
Attwood K
中科院分区：
文献类型：
--
作者：
Koochekpour S;Willard SS;Shourideh M;Ali S;Liu C;Azabdaftari G;Saleem M;Attwood K
前列腺癌 (PCa) 生物学中真正的种族差异被认为是解释 PCa 差异的潜在原因之一。没有动物模型能够代表人类 PCa 的所有方面，更具体地说，没有可用于 PCa 差异研究的动物模型。缺乏自发转化的体外细胞模型系统一直是研究和理解非洲裔美国 (AA) 男性 PCa 生物学和临床侵袭性潜在分子机制以及激素、遗传和表观遗传因素的重大障碍。在本研究中，我们建立并表征了 E006AA-hT 细胞系，作为先前表征的原代 AA-PCa 细胞系 E006AA 的高致瘤性亚系。使用细胞分化和前列腺特异性标记、光谱核型分析、细胞系认证测定、细胞增殖和迁移测定以及体外肿瘤发生测定，完成了 E006AA-hT 细胞系的广泛表征。 E006AA-hT 的光谱核型分析显示其具有超三倍体染色体补体和与其亲本细胞相似的共同细胞遗传学变化，例如二倍体 X、缺乏 Y 染色体、染色体 5、6、8、10、17、20、21 的数量增加以及来源未知的标记染色体。此外，E006AA-hT 还在 1-5、8、9、11、13、14、17 和 18 号染色体中出现许多克隆和结构畸变，例如插入、缺失、重复和易位。E006AA-hT 细胞系显示出高度致瘤性，并且在无胸腺裸鼠和三重缺陷 SCID 小鼠中以加速生长速度产生肿瘤。沉默突变的雄激素受体 (AR-599 Ser>Gly) 不会影响 E006AA-hT 及其亲代细胞类型的增殖（功能丧失），但会减少迁移（功能获得）。这些数据支持 AR 点突变可能同时导致 PCa 细胞中不同的“功能丧失”和“功能获得”表型。 E006AA-Par 及其亚系作为唯一可用的自发转化的低致瘤性和高致瘤性原代 AA-PCa 细胞系，可用于旨在支持前列腺癌差异研究的基础和转化研究。
Genuine racial differences in prostate cancer (PCa) biology have been considered among the potential reasons to explain PCa disparities. There is no animal model to represent all aspects of human PCa and, more specifically, to be used for PCa disparity research. The lack of a spontaneously transformed in vitro cell-based model system has been a significant impediment to investigating and understanding potential molecular mechanisms, and the hormonal, genetic, and epigenetic factors underlying the biological and clinical aggressiveness of PCa in African American (AA) men. In this study, we established and characterized the E006AA-hT cell line as a highly tumorigenic subline of the previously characterized primary AA-PCa cell line, E006AA. Extensive characterization of the E006AA-hT cell line was accomplished using cytodifferentiation and prostate-specific markers, spectral karyotyping, cell line authentication assays, cell proliferation and migration assays, and in vitro tumorigenesis assays. Spectral karyotyping of E006AA-hT showed a hypertriploid chromosome complement and shared cytogenetic changes similar to its parental cells such as diploid X, absence of Y-chromosomes, numerical gains in chromosomes 5,6,8,10,17,20,21, and marker chromosomes of unknown origin. In addition, E006AA-hT also presented numerous clonal and structural aberrations such as insertion, deletion, duplication, and translocations in chromosomes 1-5, 8, 9, 11, 13, 14, 17, and 18. The E006AA-hT cell line was shown to be highly tumorigenic and produced tumors at an accelerated growth rate in both athymic nude and triple-deficient SCID mice. Silencing the mutated androgen receptor (AR-599 Ser>Gly) did not affect proliferation (loss-of-function), but decreased migration (gain-of-function) in E006AA-hT and its parental cell type. These data support that AR-point mutations may lead simultaneously to different “loss-of-function” and “gain-of-function” phenotypes in PCa cells. E006AA-Par and its subline as the only available spontaneously transformed low- and highly-tumorigenic primary AA-PCa cell lines could be used for basic and translational research aimed in supporting prostate cancer disparity research.
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影响因子：
6.6
作者：
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通讯作者：
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通讯作者：
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