AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
AZT exerts its antitumoral effect by telomeric and non-telomeric effects in a mammary adenocarcinoma model
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DOI：
10.3892/or.2016.5094
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发表时间：
2016-11-01
期刊：
影响因子：
4.2
通讯作者：
Gomez, Daniel E.
中科院分区：
文献类型：
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作者：
Armando, Romina G.;Mengual Gomez, Diego;Gomez, Daniel E.
无限的复制潜力是癌症的标志之一，这主要是由于端粒酶的活性。这种全酶维持端粒长度，在每次细胞分裂中在染色体末端添加TTAGGG重复。除了这一功能外，端粒酶还具有端粒外的作用，参与癌症促进事件。研究表明，端粒酶催化亚单位端粒酶逆转录酶（TERT）在多种信号通路中起转录调节作用。考虑到这一证据和我们的经验，叠氮胸苷（AZT）作为端粒酶活性抑制剂的研究，本研究分析了一些端粒和端粒外活动的影响。为了进行本研究，我们评估了由Wnt/β-连环蛋白途径调节的基因的转录，如c-Myc和细胞周期蛋白-D1（Cyc-D1）以及与其表达相关的细胞过程，如增殖，肌动蛋白细胞骨架的修饰，细胞迁移和乳腺癌细胞系（F3 II）的细胞周期。用AZT（600 μ M）处理15代后获得的结果证实了对端粒酶的抑制作用。关于端粒外活性，我们的结果显示c-Myc、Cyc-D1和TERT的转录分别降低了64%、38%和25%（p
Limitless replicative potential is one of the hallmarks of cancer that is mainly due to the activity of telomerase. This holoenzyme maintains telomere length, adding TTAGGG repetitions at the end of chromosomes in each cell division. In addition to this function, there are extratelomeric roles of telomerase that are involved in cancer promoting events. It has been demonstrated that TERT, the catalytic component of telomerase, acts as a transcriptional modulator in many signaling pathways. Taking into account this evidence and our experience on the study of azidothymidine (AZT) as an inhibitor of telomerase activity, the present study analyzes the effect of AZT on some telomeric and extratelomeric activities. To carry out the present study, we evaluated the transcription of genes that are modulated by the Wnt/beta-catenin pathway, such as c-Myc and cyclin-D1 (Cyc-D1) and cell processes related with their expression, such as, proliferation, modifications of the actin cytoskeleton, cell migration and cell cycle in a mammary carcinoma cell line (F3II). Results obtained after treatment with AZT (600 mu M) for 15 passages confirmed the inhibitory effect on telomerase. Regarding extratelomeric activities, our results showed a decrease of 64, 38 and 25% in the transcription of c-Myc, Cyc-D1 and TERT, respectively (p