Differential Expression of ETS Family Transcription Factors in NCCIT Human Embryonic Carcinoma Cells upon Retinoic Acid-Induced Differentiation

Differential Expression of ETS Family Transcription Factors in NCCIT Human Embryonic Carcinoma Cells upon Retinoic Acid-Induced Differentiation
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DOI:
10.1248/bpb.b13-00985
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发表时间:
2014-04-01
影响因子:
2
通讯作者:
Kim, Jae-Hwan
Kim, Jae-Hwan
中科院分区:
医学4区
文献类型:
--
作者:
Park, Sung-Won;Do, Hyun-Jin;Kim, Jae-Hwan

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E26转化特异性(ETS)转录因子在发育、分化、稳态、增殖和凋亡的正常和致瘤过程中发挥重要作用。为了确定生殖细胞源性癌细胞中的关键ETS因子,我们检测了27个ETS转录因子在初生和分化的NCCIT人胚胎癌细胞中的表达模式,这些细胞具有多能性和致瘤性特征。总的来说,ETS因子在NCCIT细胞中的表达相对较低。在27个ETS因子中,多瘤病毒增强子激活因子3 (PEA3)和上皮特异性ETS转录因子1 (ESE-1)的表达水平变化最为显著。Western blot分析证实了这些模式,显示分化细胞中PEA3蛋白水平降低,ESE-1蛋白水平升高。PEA3增加了s期细胞的比例,促进了细胞的生长,而ESE-1则降低了细胞的增殖潜力。这些数据表明PEA3和ESE-1可能在多能性和致瘤性胚胎癌细胞中起重要作用。这些发现有助于我们理解生殖细胞源性干细胞中致癌ETS因子在肿瘤发生和多能性相关过程中的功能。
E26 transformation-specific (ETS) transcription factors play important roles in normal and tumorigenic processes during development, differentiation, homeostasis, proliferation, and apoptosis. To identify critical ETS factor(s) in germ cell-derived cancer cells, we examined the expression patterns of the 27 ETS transcription factors in naive and differentiated NCCIT human embryonic carcinoma cells, which exhibit both pluripotent and tumorigenic characteristics. Overall, expression of ETS factors was relatively low in NCCIT cells. Among the 27 ETS factors, polyomavirus enhancer activator 3 (PEA3) and epithelium-specific ETS transcription factor-1 (ESE-1) exhibited the most significant changes in their expression levels. Western blot analysis confirmed these patterns, revealing reduced levels of PEA3 protein and elevated levels of ESE-1 protein in differentiated cells. PEA3 increased the proportion of cells in S-phase and promoted cell growth, whereas ESE-1 reduced proliferation potential. These data suggest that PEA3 and ESE-1 may play important roles in pluripotent and tumorigenic embryonic carcinoma cells. These findings contribute to our understanding of the functions of oncogenic ETS factors in germ cell-derived stem cells during processes related to tumorigenesis and pluripotency.