Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells
Androgen receptor coregulators NOCR1, TIF2, and ARA70 may account for the hydroxyflutamide insensitivity of prostate cancer cells
复制标题
雄激素受体共调节因子 NOCR1、TIF2 和 ARA70 可能是前列腺癌细胞对羟基氟他胺不敏感的原因
DOI：
10.1007/s11845-011-0714-4
复制
发表时间：
2011-07
期刊：
影响因子：
--
通讯作者：
付强
中科院分区：
文献类型：
--
作者：
汪涌;张伟;薛炜;雷永华;高靖榆;王娟英;高小平;袁建林;保庭毅;张运涛;李金清;邵晨;师长宏;刘凡;杨増悦;邱建新;李玉梅;付强
前列腺癌细胞在持续的雄激素去除治疗后可以从雄激素依赖性状态转变为雄激素非依赖性状态。然而，这种转变背后的分子机制仍不清楚。因此，我们探讨了雄激素受体（AR）相关的基因表达的变化，在这个过渡期间，在一个新的细胞model.Material和methodsProstate癌细胞连续处理与竞争性雄激素受体抑制剂hydroxyfluoride为1.5年，这产生了一个flutamide不敏感的LNCaP亚系，LNCaP-流感，证实了MTT法，流式细胞术，和电子显微镜。我们分析了在LNCaP-flu细胞和LNCaP细胞基因表达的差异，使用基因芯片和后续RT-PCR.ResultsOver 2,428基因差异表达这些细胞系之间：1,194下调和1,234上调。有三个基因被认为与雄激素依赖性转变有关：NCOR 1、TIF 2（NCOA 2）和ARA 70（NCOA 4）。雄激素受体或前列腺特异性抗原的表达没有明显的变化。ConclusionARs和相关的coregulators在前列腺癌细胞的氟他胺不敏感的过渡中发挥着核心作用。虽然AR表达在这个转变过程中没有改变，但AR辅助调节因子的改变可能是抗雄激素不敏感性发生的关键因素。
IntroductionProstate cancer cells can switch from an androgen-dependent state to an androgen-independent state after a continuous androgen ablation therapy. However, the molecular mechanisms underlying this switch are still unclear. Therefore, we explored the change in androgen receptor (AR)-related gene expression during this transition in a novel cell model.Material and methodsProstate cancer cells were continuously treated with competitive androgen receptor inhibitor hydroxyflutamide for 1.5 years, which yielded an flutamide-insensitive LNCaP subline, LNCaP-flu, as confirmed by MTT assays, flow cytometry, and electron microscopy. We analyzed the differences in gene expression in LNCaP-flu cells and LNCaP cells using gene chips and follow-up RT-PCR.ResultsOver 2,428 genes were differentially expressed between these cell lines: 1,194 were down-regulated and 1,234 were up-regulated. Three genes in particular were considered related to the androgen-dependent transition: NCOR1, TIF2 (NCOA2), and ARA70 (NCOA4). There were no apparent changes in expression of the androgen receptor or prostate-specific antigen.ConclusionARs and associated coregulators play a central role in the flutamide-insensitive transition of prostate cancer cells. Although AR expression does not change during this transition, the change in AR coregulators may be a critical factor in the development of antiandrogen insensitivity
登录
查看更多内容
影响因子：
120.7
作者：
Leitzmann, MF;Platz, EA;Giovannucci, E
通讯作者：
Giovannucci, E
影响因子：
2.1
作者：
Drummond, F. J.;Carsin, A. -E.;Comber, H.
通讯作者：
Comber, H.
影响因子：
2.9
作者：
Wang, Y;Shao, C;Shao, GX
通讯作者：
Shao, GX
影响因子：
1.1
作者：
F. Herranz Amo;F. Arias Fúnez;M. Arrizabalaga Moreno;F. J. Calahorra Fernández;J. C. Carballido Rodríguez;R. Diz Rodríguez;J. A. Herrero Payo;C. Llorente Abarca;J. M. Martín Martínez;L. Martínez-Piñeiro Lorenzo;R. Mínguez Martínez;J. Moreno Sierra;A. Rodríguez Antolín;J. T. Tamayo Ruíz;J. Turo Antona
通讯作者：
F. Herranz Amo;F. Arias Fúnez;M. Arrizabalaga Moreno;F. J. Calahorra Fernández;J. C. Carballido Rodríguez;R. Diz Rodríguez;J. A. Herrero Payo;C. Llorente Abarca;J. M. Martín Martínez;L. Martínez-Piñeiro Lorenzo;R. Mínguez Martínez;J. Moreno Sierra;A. Rodríguez Antolín;J. T. Tamayo Ruíz;J. Turo Antona
影响因子：
11.2
作者：
C. Sonnenschein;N. Olea;M. Pasanen;A. Soto
通讯作者：
C. Sonnenschein;N. Olea;M. Pasanen;A. Soto