Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data.
Differential gene expression in tamoxifen-resistant breast cancer cells revealed by a new analytical model of RNA-Seq data.
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DOI：
10.1371/journal.pone.0041333
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wu R
中科院分区：
文献类型：
--
作者：
Huber-Keener KJ;Liu X;Wang Z;Wang Y;Freeman W;Wu S;Planas-Silva MD;Ren X;Cheng Y;Zhang Y;Vrana K;Liu CG;Yang JM;Wu R
对广泛使用的雌激素受体(ER)拮抗剂他莫昔芬()的耐药性是乳腺癌治疗成功的常见障碍。虽然的辅助治疗显著降低了疾病的复发率和死亡率，但治疗的患者中有三分之一在治疗后5年内出现复发。更好地了解与抗性相关的基因表达变化将有助于绕过这一问题。利用下一代测序方法和新的生物信息学模型，我们比较了敏感和耐药乳腺癌细胞的转录本，以寻找与耐药相关的基因。我们鉴定了1215mRNA和513个小RNA转录本在ERα功能、细胞周期调控、转录/翻译和线粒体功能障碍中的差异表达。在多个水平的基因调控中发现的变化程度突显了耐药细胞调节全球基因表达的能力。耐药细胞中小核仁核仁核糖核酸、氧化磷酸化和增殖过程的变化为对抗这种抗雌激素药物耐药性的诊断和治疗工具开发提供了领域。
Resistance to tamoxifen (Tam), a widely used antagonist of the estrogen receptor (ER), is a common obstacle to successful breast cancer treatment. While adjuvant therapy with Tam has been shown to significantly decrease the rate of disease recurrence and mortality, recurrent disease occurs in one third of patients treated with Tam within 5 years of therapy. A better understanding of gene expression alterations associated with Tam resistance will facilitate circumventing this problem. Using a next generation sequencing approach and a new bioinformatics model, we compared the transcriptomes of Tam-sensitive and Tam-resistant breast cancer cells for identification of genes involved in the development of Tam resistance. We identified differential expression of 1215 mRNA and 513 small RNA transcripts clustered into ERα functions, cell cycle regulation, transcription/translation, and mitochondrial dysfunction. The extent of alterations found at multiple levels of gene regulation highlights the ability of the Tam-resistant cells to modulate global gene expression. Alterations of small nucleolar RNA, oxidative phosphorylation, and proliferation processes in Tam-resistant cells present areas for diagnostic and therapeutic tool development for combating resistance to this anti-estrogen agent.
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影响因子：
14.9
作者：
Huang W;Umbach DM;Vincent Jordan N;Abell AN;Johnson GL;Li L
通讯作者：
Li L
DOI：
10.1126/science.1211811
发表时间：
2011-12-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Ioannidis JP;Khoury MJ
通讯作者：
Khoury MJ
DOI：
10.1093/bfgp/elm034
发表时间：
2007-12-01
期刊：
Briefings in Functional Genomics & Proteomics
影响因子：
--
作者：
Cordero, Francesca;Botta, Marco;Calogero, Raffaele A.
通讯作者：
Calogero, Raffaele A.
影响因子：
45.3
作者：
Gutierrez, MC;Detre, S;Dowsett, M
通讯作者：
Dowsett, M
影响因子：
20.3
作者：
Jia, L;Kelsey, SM;Newland, AC
通讯作者：
Newland, AC